心搏暂停和心动过速依赖性尖端扭转性室速 Locati EH et al, JACC 1992

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1 心搏暂停和心动过速依赖性尖端扭转性室速 Locati EH et al, JACC 1992
Quinindine increased the late component of the QT interval (QTU wave) and favor the onset of torsades-de-pointes following a short-long sequence. Locati EH et al, JACC 1992

2 奎尼丁增加QT间期晚电位（QTU波），在快慢搏动后诱发尖端扭转性室速。

3 红霉素对心肌电位和心电图的影响 Other non-cardiac drugs, such as Erithromicine, can have major effect on QT interval duration. Several of such drugs can interact and have addictive effects potentially very dungerous (e.g., antiarrhythmic + antidepressant + antibiotics + diuretics inducing hypokalemia)

4 其他非心脏病药物，如红霉素主要对QT间期产生影响，某些药物之间发生相互作用，对心脏产生严重的不良反应（如抗心律失常药＋抗抑郁药＋抗生素＋可诱发低钾血症的利尿剂）

5 Bartter综合征 低钾(K+ 3.7 mEq/l) M.M, 男, 17岁 Locati EH, 2000
QTc interbal is prolonged in its late component in a young mane with idiopathic potassion depletion due to Bartter’syndrome, and frequent polymorphic unsustained ventricular tachycardias are also observed. M.M, 男, 17岁 Locati EH, 2000

6 一年轻Bartter综合征患者因自发性低钾血症致晚期QTc 延长，频发非持续性多形性室速。

7 血透前后离子成分的变化及心室肌复极化改变
血透前 血透后 p QRS (msec) ns RR (msec) ns QT (msec) <0.05 QTc (msec) <0.0005 DQTc max-min <0.01 QTc_CV <0.01 K+ (mEq/l) <0.0001 Mg+2 (mEq/l) <0.0001 During hemodyalisis, fast K+ and Mg++ decrease are observed, with modest but uniform increase of QT and QTc interval duration and QT dispersion.

8 血透过程中K+ 和 Mg2＋快速降低，QTc间期及QT离散度均轻度增加。

9 血透过程中QTc 和QT 离散度的改变 300 320 340 360 380 400 420 440 460 480 500 520 540 p=0.002 20 40 60 80 100 120 140 160 180 200 220 240 260 p=0.004 (msec) QTc (msec) QTc max-min Individual changes of QTc and QT dispersion in 30 normal subjects during hemodyalis. PRE-HD POST-HD n=30 PRE-HD POST-HD n=30

10 钠、钾离子通道阻滞剂 致心律失常作用可能有使用-依赖效应 心率增快时阻滞更广 心率增快时心室传导过度延缓（  QRS)
心率增快时心室复极化过度延缓( QT)  上述效应可能与β受体阻滞剂有关

11 基线 奎尼丁 QT 340 ms QTc 347 ms QT 380 ms QTc 388 ms MG,女性, 65岁
Effect of Quinindine on QT and QTc interval duration and QT morphology at the same cycle lenght in the same normal subject. MG,女性, 65岁 Locati EH, 2005

12 同一正常个体的相同心动周期中，奎尼丁对QT、QTc间期和QT形态的影响

13 奎尼丁 阻滞活化的Ikr 心动过速时阻滞效应 更为明显，与使用-依赖 效应相一致。

14 基线 奎尼丁 R-R 最低 710 ms R-R最高 980 ms MG, Female, 65 yrs
As expected from the use-dependent effect of Quinindine, in a normal subject the blockage is more evident at faster heart rates, and QT and QTc interval prolongation are more evident at shorter cycle lenghts 奎尼丁 MG, Female, 65 yrs Locati EH et al, JACC 1998

15 此例正常个体，心率越快，奎尼丁的阻滞作用越明显，且在短心动周期中QT 及 QTc间期的延长更明显，验证了奎尼丁的“使用-依赖效应”

16 QT 间期的心率依赖性 基线 奎尼丁 MG, Female, 65 yrs Locati EH et al, JACC 1998
Therefore the slope of the QT/RR regression, particularly QTend/RR relation, is greatly reduced by Quinidine, and the regression id no longer linear. QTe/RR 0.21, QTec 431 ms QTa/RR 0.26, QTac 363 ms QTe/RR 0.12, QTec 461 ms QTa/RR 0.24, QTac 374 ms MG, Female, 65 yrs Locati EH et al, JACC 1998

17 因此，QT/RR 回归斜率尤其是QTend/ RR的相关性，在使用奎尼丁后显著降低， 并呈现非线性回归。

18 索它洛尔的反使用－依赖效应 Shimizu W et al, Am J Cardiol 1996
Opposite, sotalol (and amiodarone) show a reverse use-dependent effect, with longer QT interval duration at longer cycle lenghts (low heart rates) Shimizu W et al, Am J Cardiol 1996

19 不同抗心律失常药物对正常个体QTend/RR 及QTapex/RR 的效应
（下张幻灯显示）。

20 使用不同抗心律失常药物后的心率－依赖性QT间期
双异丙吡胺 Slope = 0.23 r = 0.80 QTc 501 ms 普罗帕酮 Slope = 0.35 r = 0.85 QTc 493 ms 胺碘酮 Slope = 0.19 r = 0.84 QTc 464 ms Effect of different antiarrhythmic drugs on QTend/RR and QTapex/RR in normal subjects 索它洛尔 Slope = 0.28 r = 0.53 QTc 445 ms

21 QT间期的动态调节 心率 性别 昼夜节律趋势 自主神经系统 药物（抗心律失常药/非抗心律失常药） 代谢紊乱 (K+, Ca++ )
心肌缺血 编码心血管离子通道的基因突变

22 心梗后伴或不伴恶性室性心律失常者QTc的昼夜变异
IMA后伴室颤/室速者 In post-IMA patients, particularly in those with histiry of malignant ventricular arrhythmias, an increased QTc interval duration and QTc variability (QTc peaks) are observed. IMA后不伴室颤/室速者 Bayes de Luna, Am Heart J 1997

23 IMA后的患者，尤其是有恶性室性心律失常发作史者，可以观测到QTc和QTc变异性(QTc 峰值) 的增加。

24 心梗后患者分别接受安慰剂（虚线）和美托洛尔（实线）治疗后
的QT/RR 回归关系 Also QT/RR relation is modified aftere myocardial infarction, with lower slope (lesser shortening of QT interval during faster heart rates, solid lines), but data in this area are still scanty and controversial. Hintze et al, ANE 1997

25 心梗后患者的QT/RR 回归关系同样受药物影响，美托洛尔组斜率降低（与虚线相比，实线所示：心率增快时， QT间期的缩短较少），但这方面的数据资料较少且尚存在争议。

26 QT间期的动态调节 心率 性别 昼夜节律趋势 自主神经系统 药物（抗心律失常药/非抗心律失常药） 代谢紊乱 (K+, Ca++ )
心肌缺血 编码心血管离子通道的基因突变

27 动作电位时程、离子电流和基因突变 Priori SG et al, Eur Heart J 1999 Current
Single mutations interfere with the activity of specific ionic corrents in different phases of the action potential. As an example, an HERG mutation modifies the acftivity of the IKr current active in the later phase of ventricular repolarization. Priori SG et al, Eur Heart J 1999

28 单一突变可影响动作电位时相特异性离子流的活性，如HERG的突变可调节心室复极晚期IKr离子流的活性。

29 不同基因型的长QT综合征患者运动试验中的
QT-RR关系 The capacity of adaptation of QT interval to cycle lenght changes during stress test which is then different in the distinct genetic variants of long QT syndrome (LQTS). This is particularly evident in LQT3 variant, with SCN5A mutation and altered Na+ currents, which shows a greater-than-normal shortening of QT interval at increasing heart rates. Schwartz et al, Circulation 1995

30 运动试验中，不同基因型的长QT综合征患者，其QT间期随心动周期长短变化的能力不同。这在3型长QT综合征尤为明显，此类患者SCN5A基因突变改变了Na+ 电流，表现为心率增快时QT间期缩短较正常人更为明显。

31 LQTS患者24小时动态心电图监测到的QT间期 和心动周期的关系
QT 间期 (ms) Then the QT/RR slopes in LQTS are different than in normal subjects, with different slopes among the distinct genetic variants. 对照 RR间期 (ms)

32 LQTS患者QT/RR斜率与正常个体不同，且不同基因型的LQTS斜率也不同。

33 LQTS患者心率-依赖性QT间期 LQT1患者 LQT2患者 LQT3患者 KVLQT1突变 HERG突变 SCN5A突变
The QT/RR relation has different slopes in the distinct genetic variants,, with flatter slopes in LQT1 (lesser QT shortening at fast heart rates) and steeeper slopes in LQT3 (greater QT shortening at fast heart rates, greater QT prolongation at low heart rates). KVLQT1突变 HERG突变 SCN5A突变

34 不同基因型的LQT综合征的QT/RR 斜率不同，LQT1斜率较平 (心率增快时QT缩短较少)，LQT3斜率较陡(心率增快时QT缩短较多，心率减慢时QT延长较多)。

35 不同基因型LQT综合征患者QT昼夜变异性
As expected, greater QTc prolongation is observed during night (at lower heart rates) in LQT3 subjects, who generally have events during sleep, while greater QT prolongation is oberved during day (at highr heart rates) in LQT1 subjects, who usually have events during activity or emotions. Stramba Badiale et al, It Heart J 2000

36 LQT3患者的夜间(心率较慢时)QTc延长更显著，此类患者多在夜间睡眠时发生心脏不良事件；LQT 1患者，白天(心率较快时) QTc延长更显著，此类患者多在活动或激动时发生心脏不良事件，这一现象与我们的预期结果一致。

37 QT 动态变化的临床应用 ü 检测抗心律失常药和非心脏病药物的 促心律失常效应 评价先天性离子通道病（ LQTS）
筛选具有发生恶性心律失常潜在危险的患者 检测抗心律失常药和非心脏病药物的 促心律失常效应 评价先天性离子通道病（ LQTS）