Correlation Between Beat‐to‐Beat QT Interval Variability and Impaired Left Ventricular Function in Patients with Previous Myocardial Infarction

Background: Beat‐to‐beat QT interval variability (QTV) is associated with sudden cardiac death and New York Heat Association functional class severity. We sought to evaluate the relationship between QTV and left ventricular (LV) function in patients with previous myocardial infarction (MI). Methods: Fifty‐nine patients with previous anterior MI were enrolled. LV ejection fraction (EF), LV end‐systolic volume index (LVESVI), and LV end‐diastolic volume index (LVEDVI) were measured by LV contrast angiography. QT interval was measured by automated analysis of 512‐beat records of 12‐lead electrocardiogram. The mean interval, standard deviation and variance in RR and QT intervals, and the QT variability index (QTVI) were calculated for each patient using two leads that corresponded with and without the infarction site. High‐frequency power, low‐frequency power, total‐frequency power, and the ratio of low‐frequency to high‐frequency power in RR and QT intervals were calculated. Results: While measured indices of RR intervals and indices of QT intervals, which did not correspond with the infarction site, did not correlate with differences in LV function, measured indices of QT intervals, which corresponded with the infarction site, did correlate with differences in LV function. However, there were no correlations between the ratio of low‐frequency to high‐frequency power in QT intervals and EF or LVEDVI. Correlations between QTVI and LV function were observed, particularly between QTVI and LVESVI (r = 0.712, P < 0.0001). Conclusion: In patients with previous anterior MI, there was variability in temporal dispersion of QT interval and a strong correlation between QTV corresponded with the infarcted site and LV function.     

陈旧性心肌梗死室性早搏与QT离散度及心率变异性的关系

目的:探讨陈旧性心肌梗死(OMI)患者室性早搏Lown's分级与QT离散度及心率变异性(HRV)的关系。方法:82例OMI患者,按室性早搏Lown's级别分组:A组:Lown's 1-3级,60例;B组:Lown's 4-5级,22例;检测各组HRV时域指标和QTd,并与正常对照组比较。结果:(1)A组的QTd与正常对照组比较无显著差异(P>0.05);而B组的QTd显著增加,明显大于A组和正常对照组(P<0.01);(2)与正常对照组和A组比较,B组的HRV各项时域参数指标显著降低(P<0.001)。结论:室性早搏Lown's 4-5级OMI患者的QTd明显增大、HRV显著降低;预示其发生恶性室性心律失常的危险性增高。     

Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome

Introduction: One form of the hereditary long‐QT syndrome, LQT3‐ΔKPQ, is associated with sustained inward sodium current during membrane depolarization. Ranolazine reduces late sodium channel current, and we hypothesized that ranolazine would have beneficial effects on electrical and mechanical cardiac function in LQT3 patients with the SCN5A‐ΔKPQ mutation. Methods: We assessed the effects of 8‐hour intravenous ranolazine infusions (45 mg/h for 3 hours followed by 90 mg/h for 5 hours) on ventricular repolarization and myocardial relaxation in 5 LQT3 patients with the SCN5A‐ΔKPQ mutation. Changes in electrocardiographic repolarization parameters from before to during ranolazine infusion were evaluated by time‐matched, paired t‐test analyses. Cardiac ultrasound recordings were obtained before ranolazine infusion and just before completion of the 8‐hour ranolazine infusion. Results: Ranolazine shortened QTc by 26 ± 3 ms (P < 0.0001) in a concentration‐dependent manner. At peak ranolazine infusion, there was a significant 13% shortening in left ventricular isovolumic relaxation time, a significant 25% increase in mitral E‐wave velocity, and a meaningful 22% decrease in mitral E‐wave deceleration time compared with the baseline. No adverse effects of ranolazine were observed in the study patients. Conclusion: Ranolazine at therapeutic concentrations shortened a prolonged QTc interval and improved diastolic relaxation in patients with the LQT3‐ΔKPQ mutation, a genetic disorder that is known to cause an increase in late sodium current.     

Young adults born small for gestational age: Is reduced baroreceptor sensitivity a risk factor for hypertension?

BACKGROUND. Adults born small for gestational age (SGA) are at increased risk for the metabolic syndrome and cardiovascular disease. HYPOTHESIS: Impaired short-term blood pressure regulation may contribute to the development of hypertension in patients born SGA. METHODS: In all, 43 patients born SGA (18 female, age 19.4 +/- 0.3 years) were evaluated by beat-to-beat blood pressure and heart rate registration during rest and mental and orthostatic stress. The study group was divided into Group 1 with normal resting blood pressure (n=32) and Group 2 with slightly elevated blood pressure (n=11). Baroreceptor sensitivity (BRS) was calculated. Fasting insulin as well as lipid levels were correlated with hemodynamic parameters. RESULTS: Eleven of the 43 study patients (25%) had a slightly elevated resting systolic blood pressure (SBP) rising during mental and orthostatic stress. Body mass index (BMI) and fasting insulin levels correlated strongly with SBP in Group 2. Baroreceptor sensitivity was lower in Group 2 at rest (p < 0.05). CONCLUSIONS: Three components of metabolic syndrome (elevated BP, high BMI, elevated insulin levels) correlate strongly in young adolescents born SGA; BRS is reduced in prehypertensive patients. Close follow-up is warranted during adult life as they are predisposed for developing a metabolic syndrome with elevated cardiovascular risk.     

室性期前收缩患者心室复极储备功能评价

目的探讨QTc间期、QTd、Tp-ec间期、Tp-ed、Tp-e/QT比值对室性期前收缩患者复极储备功能的评价作用。方法入选窦性心律合并室性期前收缩患者229例,根据室性期前收缩后窦性心动周期中QT间期的恢复,将恢复异常者纳入观察组,将恢复正常者纳入对照组,比较组间QTc间期、QTd、Tp-ec间期、Tp-ed、室速发作的差异性;比较组内不同心率下QTc间期的变化;评价QTc间期、QTd、Tp-ec间期、Tp-ed、Tp-e/QT比值对室性期前收缩患者心室复极异常的诊断价值。结果观察组与对照组间性别、年龄、QTd无统计学差异,QTc间期(p=0.0100.05)、Tp-ec间期(p=0.0000.05)、Tp-ed(p=0.030.05)有统计学差异,室速发作(17例、5例),发生率(p=0.0030.05)有统计学差异;观察组、对照组不同心率下QTc间期变化有统计学差异;QTc、Tp-ec、Tp-e/QT比值对复极异常有诊断价值(p0.05),QTd、TP-ed、对复极异常无诊断价值(p0.05),各指标诊断复极储备异常的最佳界值如下:男性QTc≥458ms,女性QTc≥469ms,Tp-ec≥95ms,TP-e/QT比值≥0.22。结论 QTc、QTd、TP-e、TP-ed、TP-e/QT比值是适用于评价室性期前收缩患者心室复极储备功能异常的无创性指标,结合室性期前收缩后QT间期的动态性变化可提高诊断的准确度。对SCD高危人群的早期诊断及预防性治疗有指导作用。     

Bias of QT Dispersion

Background: Prolonged QT dispersion (QID) is associated with an increased risk of arrhythmic death but its accuracy varies substantially between otherwise similar studies. This study describes a new type of bias that can explain some of these differences. Material: One dataset (DiaSet) consisted of 356 subjects: 169 with diabetes, 187 nondiabetic control persons. Another dataset (ArrSet) consisted of 110 subjects with remote myocardial infarction: 55 with no history of arrhythmia and 55 with a recent history of ventricular tachycardia or fibrillation. Methods: 12‐lead surface ECGs were recorded with an amplification of 10 mm/mV at a paper speed of 50 mm/s. The QT interval was measured manually by the tangent‐method. The bias depends on the magnitude of the measurement errors and the measurable part of the bias increases with the number of the repeated measurements of QT. Results: The measurable bias was significant for both datasets and decreased for increasing QTD in the DiaSet (P < 0.001) and in the ArrSet (P = 0.11). The bias was 2.5 ms and 1.9 ms at QTD = 38 ms and 68 ms, respectively, in the ArrSet, and 7.5 ms and 2.8 ms at QTD = 19 ms and 55 ms, respectively, in the DiaSet. Conclusions: This study shows that random measurement errors of QT introduces a type of bias in QTD that decreases as the dispersion increases, thus reducing the separation between patients with low versus high dispersion. The bias can also explain some of the differences in the mean QTD between studies of healthy populations. Averaging QT over three successive beats reduces the bias efficiently. A.N.E. 2001;6(1):38–42     

Common candidate gene variants are associated with QT interval duration in the general population

Objectives. QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30–40% of the QT‐interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population‐based sample. Methods. We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5043 Finnish individuals, using Sequenom MALDI‐TOF mass spectrometry. ECG parameters were measured from digital 12‐lead ECGs and QT intervals were adjusted for age, gender and heart rate with a nomogram (Nc) method derived from the present study population. Results. The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QT_Nc interval (P = 3.6 × 10^?11) in gender‐pooled analysis. In agreement with previous studies, we replicated the association with QT_Nc interval with minor alleles of KCNH2 intronic SNP rs3807375 [1.6 ms (SE 0.4) or 0.08 SD, P = 4.7 × 10^?5], KCNH2 K897T [?2.6 ms (SE 0.5) or ?0.14 SD, P = 2.1 × 10^?7] and NOSA1P variants including rs2880058 [4.0 ms (SE 0.4) or 0.22 SD, P = 3.2 × 10^?24] under additive models. Conclusions. We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age‐, gender‐ and heart rate‐adjusted QT interval and could thus modulate repolarization‐related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.     

The prognostic value of QTc interval and QT dispersion following myocardial infarction in patients treated with or without dofetilide

BACKGROUND: Acute myocardial infarction (MI) is associated with an increased risk of death, with a 1-year mortality close to 10% in patients discharged from hospital alive. During the first year following MI, close to 50% of deaths are assumed to be due to arrhythmic events. HYPOTHESIS: The study was undertaken to determine the interaction between dofetilide treatment and pretreatment QTc interval and QT dispersion regarding mortality in patients with left ventricular (LV) dysfunction and a recent MI. METHODS: The study population consisted of 894 patients with a recent MI and LV systolic dysfunction, who were randomized to receive dofetilide or placebo. The study was a substudy of the Danish Investigations of Arrhythmia and Mortality on Dofetilide-MI (DIAMOND-MI). RESULTS: During a minimum of 1-year follow-up, 261 (29%) patients died. Baseline QTc interval did not hold any prognostic value on mortality for placebo-treated patients. When pretreatment QTc interval was <429 ms, dofetilide resulted in a 45% reduction of mortality (hazard ratio 0.55, 95% confidence limits 0.34-0.88, p<0.02) compared with placebo. When QTc interval was >429 ms, dofetilide did not influence mortality significantly. This study revealed no statistically significant relation between QT dispersion, dofetilide treatment, and mortality. CONCLUSION: In patients with a recent MI, LV dysfunction, and a short baseline QTc interval, dofetilide is associated with significant survival benefit. This benefit is not seen with a longer QTc interval. QT dispersion is not a risk factor in this population.     

Phenotypic Variability in Caucasian and Japanese Patients with Matched LQT1 Mutations

Background : Ethnic differences may affect the phenotypic expression of genetic disorders. However, data regarding the effect of ethnicity on outcome in patients with genetic cardiac disorders are limited. We compared the clinical course of Caucasian and Japanese long QT type‐1 (LQT1) patients who were matched for mutations in the KCNQ1 gene. Methods : The study population comprised 62 Caucasian and 38 Japanese LQT1 patients from the International LQTS Registry who were identified as having six identical KCNQ1 mutations. The biophysical function of the mutations was categorized into dominant‐negative (>50%) or haploinsufficiency (≤50%) reduction in cardiac repolarizing IKs potassium channel current. The primary end point of the study was the occurrence of a first cardiac event from birth through age 40 years. Results : Japanese patients had a significantly higher cumulative rate of cardiac events (67%) than Caucasian patients (39%; P = 0.01). The respective frequencies of dominant negative mutations in the two ethnic groups were 63% and 28% (P < 0.001). In multivariate analysis, Japanese patients had an 81% increase in the risk of cardiac events (P = 0.06) as compared with Caucasians. However, when the biophysical function of the mutations was included in the multivariate model, the risk associated with Japanese ethnicity was no longer evident (HR = 1.05; P = 0.89). Harboring a dominant negative mutation was shown to be the most powerful and significant predictor of outcome (HR = 3.78; P < 0.001). Conclusions : Our data indicate that ethnic differences in the clinical expression of LQTS can be attributed to the differences in frequencies of the specific mutations within the two populations.     

Sudden Paradoxical QT‐Interval Prolongation Exacerbating T‐Wave Alternans in a Patient with Type 3 Long QT Syndrome

We report a case with type 3 congenital long QT syndrome, who exhibited a sudden paradoxical QT‐interval prolongation during a progressive increase in heart rate, which exacerbated T‐wave alternans.     

期前收缩后窦性搏动ST-T改变的临床意义

目的：探讨期前收缩后窦性搏动 Ｓ Ｔ Ｔ 改变的发生机理。方法：对房性期前收缩４０例,室性期前收缩７８例。按期前收缩后窦性搏动有无 Ｓ Ｔ Ｔ 改变分为两组（有改变的８０例,无改变的３８例）进行对比分析。结果：期前收缩后的窦性搏动 Ｓ Ｔ Ｔ 改变与心电图各间期的长短无关（ Ｐ ＞ ０．０５）,但室性期前收缩后的 Ｓ Ｔ Ｔ 改变与室性期前收缩的配对间期有关（即提前量）,室性期前收缩的两组比较 Ｐ ＜ ０．０５。期前收缩后回转周期的长短对 Ｓ Ｔ Ｔ 改变亦有影响,但无统计学差异。结论：期前收缩后窦性搏动的 Ｓ Ｔ Ｔ 改变的机制可能与电张力调整有关,是否与基础心脏病或心肌缺血有关尚待进一步研究。     

Effects of Glucose‐Insulin‐Potassium Infusion on QT Dispersion in Patients with Acute Myocardial Infarction

Background: Increased QT dispersion during acute myocardial infarction (AMI) has been associated with the occurrence of ventricular arrhythmias. Also, serum potassium levels have been shown to be relevant to the arrhythmic risk in this group of patients. The aim of the present study was to assess changes in QT dispersion during infusion of glucose‐insulin‐potassium (GIK) during AMI. Methods: Patients from the Pol‐GIK study were analyzed retrospectively. The patients were selected from the placebo (1000 ml of 0.89% NaCI) and the GIK (1000 ml of 10% dextrose, 20–32 units of insulin, 80 mEq K+) groups (18 and 24 patients, respectively). QT interval duration and dispersion the difference between the longest and shortest QT intervals) were measured at baseline, 18–24 hours into placebo/GIK infusion and 24 hours after the end of infusion. Results: In the placebo group, plasma potassium levels changed from 4.1 ± 0.5 mmol/L at baseline to 4.6 ± 0.8 mmol/L during infusion (P < 0.05) and 4.6 ± 0.4 mmol/L after infusion, whereas in the GIK group the respective values were 4.0 ± 0.4, 4.6 ± 0.3 (P < 0.0001), and 4.5 ± 0.5 mmol/L. QT interval duration was stable throughout the study and there was no difference between the groups. The two groups did not differ in respect to QT dispersion at any time point, the respective values were 79 ± 28, 65 ± 25, and 77 ± 27 ms in the placebo group, and 61 ± 35, 60 ± 26, and 76 ± 43 ms in the GIK group. The incidence of arrhythmias was also similar in both groups. Conclusions: GIK, at the dose used, is unlikely to affect heterogeneity of ventricular repolarization during AMI. A.N.E. 2001;6(1)50–54