Arrhythmia Service, Division of Cardiology, University of Western Ontario, London, Ontario, Canada.
Circ Arrhythm Electrophysiol. 2010 Apr;3(2):120-5. doi: 10.1161/CIRCEP.109.907865. Epub 2010 Jan 9.
The clinical diagnosis of long-QT syndrome (LQTS) remains challenging when ECG abnormalities are borderline or intermittent. Despite issues with access, cost, and heterogeneity of LQTS mutations, genetic testing remains the diagnostic gold standard for diagnosis of LQTS. We sought to develop a provocative testing strategy to unmask the LQTS phenotype and relate this to the results of genetic testing.
From 1995 to 2008, 159 consecutive patients with suspected LQTS underwent provocative testing that consisted of a modified Bruce protocol treadmill exercise test, with ECGs recorded supine at rest, immediately on standing, and at 1-minute intervals during exercise, at peak exercise, and at 1-minute intervals during the recovery phase. Similar testing was carried out on a stationary bike in a gradual and burst exercise fashion. LQTS was confirmed with genotyping in all 95 affected LQTS patients and excluded with negative family screening in 64 control subjects. Patients were studied before and after initiation of beta-blockers. Of 159 patients, 50 had an LQT1 mutation and 45 had an LQT2 mutation. In the LQTS group, 44.3% of patients had a normal-to-borderline resting QTc interval. LQTS patients exhibited a greater prolongation in QTc with postural change than unaffected patients (LQT1: 40 ms [IQR, 42]; LQT2: 35 ms [IQR, 46]; and LQTS-negative: 21 ms [IQR, 37]; P=0.029). During exercise, LQT1 patients had marked QTc prolongation compared with LQT2 and LQTS-negative patients (LQT1: 65 ms [60], LQT2: 3 ms [46], LQTS negative: 5 ms [41]; P<0.0001). QT hysteresis was more pronounced in patients with LQT2 mutations compared with LQT1 and LQT-negative patients (LQT2: 40 ms [10], LQT1: 15 ms [40]; LQTS-negative: 20 ms [20]; P<0.001). beta-Blockade normalized the QTc changes seen with standing and QT hysteresis.
The presence and genotype of LQTS can be predicted by a combination of postural and exercise changes in the QT/RR relationship. beta-Blockade normalized these changes. Routine exercise testing is useful in predicting and directing genetic testing in LQTS.
当心电图异常呈边界性或间歇性时，长 QT 综合征（LQTS）的临床诊断仍然具有挑战性。尽管存在获取、成本和 LQTS 突变异质性等问题，但基因检测仍然是诊断 LQTS 的诊断金标准。我们试图制定一种激发试验策略来揭示 LQTS 表型，并将其与基因检测结果相关联。
1995 年至 2008 年，159 例疑似 LQTS 的连续患者接受了激发试验，该试验包括改良的 Bruce 方案跑步机运动试验，在休息时仰卧位记录心电图，立即站立，在运动期间、达到峰值运动时和恢复阶段的 1 分钟间隔记录心电图。在逐渐和突发运动方式的固定自行车上进行类似的测试。在 95 例确诊的 LQTS 患者中，所有患者均通过基因分型证实 LQTS，在 64 例对照患者中，通过阴性家族筛查排除 LQTS。在开始使用β受体阻滞剂之前和之后对患者进行了研究。在 159 例患者中，50 例有 LQT1 突变，45 例有 LQT2 突变。在 LQTS 组中，44.3%的患者静息 QTc 间期正常至边界性。与未受影响的患者相比，LQTS 患者体位变化时 QTc 延长更大（LQT1：40 ms [IQR，42]；LQT2：35 ms [IQR，46]；LQTS 阴性：21 ms [IQR，37]；P=0.029）。在运动期间，与 LQT2 和 LQTS 阴性患者相比，LQT1 患者的 QTc 延长更为明显（LQT1：65 ms [60]，LQT2：3 ms [46]，LQTS 阴性：5 ms [41]；P<0.0001）。与 LQT1 和 LQTS 阴性患者相比，LQT2 突变患者的 QT 滞后更为明显（LQT2：40 ms [10]，LQT1：15 ms [40]；LQTS 阴性：20 ms [20]；P<0.001）。β受体阻滞剂使站立时 QTc 变化和 QT 滞后正常化。
体位和运动过程中 QT/RR 关系的变化可以预测 LQTS 的存在和基因型。β受体阻滞剂使这些变化正常化。常规运动试验可用于预测和指导 LQTS 的基因检测。
