QT Dispersion Level and Its Clinical Significance.in Dilated Cardiomyopathy

［1］Richardson CP, Mckenna RM, Bristow CM, et al.Report of the 1995 Word Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation, 1996,93: 841 ［2］Barr CS, Naas A, Freeman M, et al. QT dispersion and sudden unexpected death in chronic heart failure. Lancet, 1994,343:327 ［3］Martin AB, Garson A, Perry JC, et al. Prolonged QT interval in hypertropic and dilated cardiomyopathy in children. Am Heart J, 1994,127(1):64 ［4］Pye M, Quinn AC, Cobble SM. QT dispersion: a non-invasive marker of susceptibility to arrhythmia in patients with sustained ventricular arrhythmias?Br Heart J, 1994,71(5):51 ［5］Berger RD, Kasper EK, Baughman KL, et al. Beat to beat QT interval variability: novel evidence for repolarization lability in ischemic and non ischemic dilated cardiomyopathy. Circulation, 1997, 96 (5):1557 ［6］Wolfram G, Ulrike S, Volker M, et al. QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy. Am J Cardiol, 1997,78: 458 ［7］Fei L, Goldman JH, Prasal K, et al. QT dispersion and RR variations on 12-lead ECGs in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy. Eur Heart J, 1996,17: 258 ［8］Pan YZ, Guo NS, Xing ZF, et al. The relation between QT dispersion and ventricular arrhythmia of dilated cardiomyopathy. Chin J Inter Medi, 1996,35(11):73 ［9］Galinier M, Vialette JC, Fourcade J, et al. QT interval dispersion as a predictor of arrhythmic events in congestive heart failure. Importance of aetiology. Eur Heart J, 1998,19(7) :1054     

Comparison of the acute cardiotoxicity of the antimalarial drug halofantrine in vitro and in vivo in anaesthetized guinea-pigs

1. Several unrelated drugs have pro-arrhythmic activity associated with an ability to prolong the QT interval of the ECG. The aim of this work was to examine the effects of the antimalarial drug halofantrine in vivo and in vitro.
2. In anaesthetized guinea-pigs consecutive bolus doses of halofantrine (0.3, 1, 3, 10 and 30 mg kg⁻¹, i.v.) at 25 min intervals caused dose-dependent prolongation of the rate corrected QTc interval and bradycardia. The change in heart rate became significant after administration of 10 mg kg⁻¹ halofantrine (−23±9 beats min⁻¹) whereas the increase in QTc was significant with only 1 mg kg⁻¹ halofantrine (22±10 ms). It was only with the highest dose of halofantrine that the PR interval was increased (from 52±3 to 67±4 ms) and second degree atrioventricular (AV) block (type 1 Mobitz) occurred in all animals. No changes were observed in any parameters in a separate group of guinea-pigs which received vehicle (dimethylacetamide 60% propylene glycol 40%) at equivalent time points.
3. The blood concentrations of halofantrine ranged from 0.26±0.17 μM after administration of 0.3 mg kg⁻¹ to 2.79±0.87 μM after 30 mg kg⁻¹, i.v. There was a significant correlation between the blood concentrations of halofantrine and the changes in QTc interval.
4. In guinea-pig left papillary muscles the effective refractory period was increased significantly 60 min after addition of halofantrine; from 161±4 to 173±6 ms with 10 μM, 156±8 to 174±6 ms with 30 μM and 165±6 to 179±5 ms with 100 μM halofantrine. However, the vehicle (0.1% Tween 80 in DMSO; final concentration of vehicle in Krebs, 1%) also increased the effective refractory period from 164±5 to 173±6 ms. Similar results were obtained in right ventricular strips but left atrial effective refractory periods were not altered by either the vehicle or halofantrine.
5. The results of these experiments suggest that any direct effects that halofantrine may have had on the effective refractory period of cardiac muscle cannot be separated from those of the vehicle. The prolongation of QTc and consistent observation of AV block with halofantrine in anaesthetized guinea-pigs suggest that in vivo models may be more useful for further studies investigating the mechanisms underlying the cardiotoxicity of halofantrine.

     

急性心肌梗死早期恶性心律失常与QT JT间期离散度关系的临床分析

目的 探讨急性心肌梗死（ＡＭＩ）ＱＴ间期离散度（ＱＴＤ）、ＪＴ间期离散度（ＪＴＤ）与早期恶性心律失常的关系。方法 测量并计算ＡＭＩ体表心电图ＱＴＤ、ＪＴＤ,并与５０例正常人作对照。结果 ＡＭＩ发生恶性心律失常组ＱＴＤ,ＪＴＤ均显著大于对照组（Ｐ〉０．０１）;前壁心面梗死组的ＱＴＤ、ＪＩＴＤ明显大于下壁心肌梗死组（Ｐ〈０．０５）。结论 ＱＴＤ、ＪＴＤ增加是ＡＭＩ早期发生恶性心律失常的重要指标之一。     

胺碘酮 美西律 普罗帕酮对QT离散度影响的临床观察

目的：观察胺碘酮,美西律,普罗帕酮有效治疗室性心律失常前后QT离散度（QTd）的变化。方法：采用随机、单盲的方法,测定3组病人用药前及用药后一周或两周的QTd．QTCd及RR间期．结果：用药前3组的QTd．QTcd及RR间期无显著性差异（P＞0.05）。用药后按碘酮组的QTd,QTcd明显降低（QTd37±15ms与21±9ms,QTcd41±17ms与23±10ms．P＜0．05）,RR间期明显延长;美西律及普罗帕酮组用药前后QTd,QTcd．RR间期无显著性变化（P＞0．05）。用药后胺碘酮组的QTd．QTcd显著小于别外两组（QTd21±9ms与35±8ms,37±13ms,QTcd23±16ms与39±11ms,39±14msP＜0．05））;但RR间期显著长于另两组。结论：治疗室性心律失常有效者胺碘酮降低QT离散度．而美西律,普罗帕酮对QT离散度无显著影响。     

Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome

The long QT syndrome (LQTS) is associated with syncopal attacks or even sudden death at a young age due to ventricular fibrillation. We report a patient with an undiagnosed LQTS who had an episode of cardiac arrest during the final part of general anesthesia, immediately after the drugs for reversal of the neuromuscular blockade were given. We suggest that the administration of glycopyrronium might have been the provoking factor in this patient.     

心肌梗死患者QT间期变异性和心率变异的分析

目的　探讨 QT间期变异性 (QTV)、QT间期变异系数 (QTCV )在心肌梗死患者中的意义 ,两指标与心率变异性 (HRV)是否有联系以及联系的强度。方法　对 5 4例诊断明确的心肌梗死患者和 5 0名正常人进行 2 4 h动态心电图的 QTV、QTCV、HRV的对比分析。结果　心肌梗死患者和对照组的 QTV (2 0± 6比 2 9± 9,P=0 .0 0 0 1)和 QTCV(0 .0 5 4± 0 .0 16比 0 .0 76± 0 .0 2 4 ,P=0 .0 0 0 1)差异有显著性 ;各组中 HRV和 QTV有弱相关性 (P<0 .0 5 ) ,HRV和 QTCV无相关 (P>0 .0 5 )。结论　心肌梗死患者 QTV、QTCV减低 ,HRV的变化几乎不影响两者的变化 ,QTV和 QTCV可能成为预测心律失常的新指标     

QT and RR intervals in conscious and anesthetized guinea pigs with highly varying RR intervals and given QTc-lengthening test articles.

A facile system for obtaining electrocardiograms from conscious animals was used to conduct studies on 12 animals studied both conscious and anesthetized, on 4 conscious animals given vehicle (0.5% methylcellulose) and QT-lengthening test articles, and on 6 animals given test articles thought to not lengthen QTc. In 12 animals whose ECGs were monitored via a bipolar transthoracic ECG, heart rates were slowed with 1.0 mg/kg zatebradine, while they were conscious in their slings, and after being anesthetized with ketamine/xylazine. The following regression equations were obtained relating QT to RR: QT = 44.7 ln RR - 132.9, r2 = 0.7, for conscious animals; QT = 79.4 ln RR - 287.4, r2 = 0.8 for anesthetized animals, with RR intervals varying between 150 and 550 ms. The anesthetic increases QT at all RR intervals (p < 0.001), but does not change the slope of the relationship between QT and RR when compared with the conscious guinea pig. The Fridericia method was best for correcting QT for RR interval in conscious guinea pigs, but the Bazett method was best for correcting in anesthetized animals. QTc lengthened significantly in all conscious guinea pigs given, orally, cisapride, ketoconazole, and sotalol (positive test articles) and did not change with methylcellulose (the vehicle) or with propranolol, verapamil, or enalapril (negative controls). These techniques and relationships demonstrate that this methodology may be useful in exploring torsadogenic effects of novel pharmacological entities.     

心肌缺血对QT间期变异性的影响

目的 :探讨QT间期变异性 (QTV)在心肌缺血中的意义。方法 :对 37例动态心电图有明显心肌缺血和 42例无心肌缺血患者进行QT间期动态分析。结果 :心肌缺血组的QT间期变异性明显大于无心肌缺血组。结论 :心肌缺血影响QT间期变异性。     

Ventricular arrhythmia and torsade de pointe: Dose limiting toxicities of the MDR-modulator S9788 in a phase I trial

Background: S9788 is a triazineaminopiperidine derivative capable of reversing multidrug resistance (MDR) in vitro. In preclinical models S9788 was several fold more potent MDR inhibitor than verapamil or cyclosporine. At P-glycoprotein (Pgp) blocking concentrations, S9788 appeared to have only very little toxicity.Patients and methods: In a two step phase I trial we treated 39 patients with refractory cancer with S9788 and bolus doxorubicin. The steps differed mainly in the S9788 infusion duration; in the first part 23 patients received the MDR-reversing drug S9788 over 30 minutes, in the second step of the study 16 patients were administered S9788 over 150 minutes. The doses of S9788 were escalated in cohorts of three patients up to a dose level (DL) of 96 mg/m2 on the 30 minutes infusion, and to 144 mg/m2 on the 150 minutes infusion. The pharmacokinetics of S9788 were determined.Results: With the 30-minute infusion schedule symptomatic cardiac arrhythmia were found to be dose limiting. In all patients at the highest DL transient cardiac repolarization prolongation with a long QT-interval on ECG was demonstrated. With the 150-minute administration schedule, S9788 could be escalated up to 144 mg/m2 without subjective toxicity. However, transient QT prolongation was present in all patients. A third degree AV-block and a QT increase of about 40% occurred at the highest DL. Asymptomatic torsade de pointe (DL 96 mg/m2) was demonstrated on Holter recording in one patient. Theses repolarization disturbances with QT increase were considered dose limiting toxicity and the trial was closed. No arrhythmia related death was noted. Pharmacokinetics were similar with both infusion schedules with a mean alpha half life of 11.3 and 13.2 minutes, for the 30-minute and 150-minute infusion, and a terminal half life of 13.5 and 15 hours, respectively. QTc prolongation duration appeared to be dose-dependent.Conclusions: With the tested infusion schedules, cardiac toxicity, in particular AV-blocks and QT prolongation, leading to ventricular arrhythmia and torsade de pointe, are the dose limiting toxicities of S9788. Our experience together with the observation of asymptomatic torsade de pointe in two other phase I trials of S9788 infused over six hours precluded the further clinical development of S9788.     

单纯性肥胖儿童心电图QT离散度与左心室射血分数的关系研究

【目的】　分析单纯性肥胖儿童是否存在心电图QT离散度 (QTD ,QTcD)的改变及其可能的临床应用价值。　【方法】　测量单纯性肥胖组和对照组儿童 12导联心电图RR间期、QT间期并计算QTc、QTD、QTcD ,彩色多普勒测量受试者左室射血分数 (LEF)。　【结果】　肥胖组RR、LEF明显低于对照组 (P <0 .0 1,P <0 .0 0 1) ,QTcD明显高于对照组 (P <0 .0 5 ) ,QTD虽然比对照组大 ,但无统计学意义 (P >0 .0 5 ) ;肥胖组QTD、QTcD与LEF成负相关关系 (r = 0 .485 ,P <0 .0 5 ;r = 0 .5 12 ,P <0 .0 5 ) ,与RR成正相关关系 (r =0 .5 2 0 ,P <0 .0 2 ;r =0 .613 ,P <0 .0 0 5 )。　【结论】　肥胖儿童LEF降低 ,心率增快 ,QTcD显著延长 ;QTD、QTcD的变化可能是肥胖儿童心室肥厚、心肌脂肪浸润等某一或某几项病理改变及心率变化的综合反映 ,也是LEF变化的反映