Extramiana Fabrice, Maison-Blanche Pierre, Cabanis Marie-José, Ortemann-Renon Catherine, Beaufils Philippe, Leenhardt Antoine
Cardiology Department, Lariboisière Hospital, 2 rue Ambroise Paré, 75475 Paris Cedex 10.
Clin Pharmacol Ther. 2005 Apr;77(4):247-58. doi: 10.1016/j.clpt.2004.10.016.
The formulas for heart rate (HR) correction of QT interval have been shown to overcorrect or undercorrect this interval with changes in HR. A Holter-monitoring method avoiding the need for any correction formulas is proposed as a means to assess drug-induced QT interval changes.
A thorough QT study included 2 single doses of the alpha1-adrenergic receptor blocker alfuzosin, placebo, and a QT-positive control arm (moxifloxacin) in 48 healthy subjects. Bazett, Fridericia, population-specific (QTcN), and subject-specific (QTcNi) correction formulas were applied to 12-lead electrocardio-graphic recording data. QT1000 (QT at RR = 1000 ms), QT largest bin (at the largest sample size bin), and QT average (average QT of all RR bins) were obtained from Holter recordings by use of custom software to perform rate-independent QT analysis.
The 3 Holter end points provided similar results, as follows: Moxifloxacin-induced QT prolongation was 7.0 ms (95% confidence interval [CI], 4.4-9.6 ms) for QT1000, 6.9 ms (95% CI, 4.8-9.1 ms) for QT largest bin, and 6.6 ms (95% CI, 4.6-8.6 ms) for QT average. At the therapeutic dose (10 mg), alfuzosin did not induce significant change in the QT. The 40-mg dose of alfuzosin increased HR by 3.7 beats/min and induced a small QT1000 increase of 2.9 ms (95% CI, 0.3-5.5 ms) (QTcN, +4.6 ms [95% CI, 2.1-7.0 ms]; QTcNi, +4.7 ms [95% CI, 2.2-7.1 ms]). Data corrected by "universal" correction formulas still showed rate dependency and yielded larger QTc change estimations. The Holter method was able to show the drug-induced changes in QT rate dependence.
The direct Holter-based QT interval measurement method provides an alternative approach to measure rate-independent estimates of QT interval changes during treatment.
已证实用于校正心率（HR）对QT间期影响的公式，在HR发生变化时会出现过度校正或校正不足的情况。本文提出一种无需任何校正公式的动态心电图监测方法，作为评估药物引起的QT间期变化的手段。
一项全面的QT研究纳入了48名健康受试者，设置2个单剂量的α1肾上腺素能受体阻滞剂阿夫唑嗪组、安慰剂组以及一个QT阳性对照组（莫西沙星）。将Bazett、Fridericia、人群特异性（QTcN）和受试者特异性（QTcNi）校正公式应用于12导联心电图记录数据。通过使用定制软件进行心率独立QT分析，从动态心电图记录中获取QT1000（RR = 1000 ms时的QT）、QT最大组距（最大样本量组距时的QT）和QT平均值（所有RR组距的平均QT）。
3个动态心电图终点得出了相似的结果，如下：莫西沙星引起的QT间期延长，QT1000为7.0 ms（95%置信区间[CI]，4.4 - 9.6 ms），QT最大组距为6.9 ms（95% CI，4.8 - 9.1 ms），QT平均值为6.6 ms（95% CI，4.6 - 8.6 ms）。在治疗剂量（10 mg）下，阿夫唑嗪未引起QT的显著变化。40 mg剂量的阿夫唑嗪使心率增加3.7次/分钟，并使QT1000小幅增加2.9 ms（95% CI，0.3 - 5.5 ms）（QTcN，+4.6 ms [95% CI，2.1 - 7.0 ms]；QTcNi，+4.7 ms [95% CI，2.2 - 7.1 ms]）。通过“通用”校正公式校正的数据仍显示出心率依赖性，并产生了更大的QTc变化估计值。动态心电图方法能够显示药物引起的QT心率依赖性变化。
基于动态心电图的直接QT间期测量方法为测量治疗期间心率独立的QT间期变化估计值提供了一种替代方法。
