Role of α_1-Blockade in Congenital Long QT Syndrome : Investigation by Exercise Stress Test

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Beta-blockade is widely reported to reduce the incidence of syncope in 75-80% of patients with congenital long QT syndrome (LQTS). However, despite full-dose β-blockade, 20-25% of patients continue to have syncopal episodes and remain at high risk for sudden cardiac death. In some patients refractory to β-blockade, the recurrence of arrhythmias is successfully prevented by left stellate ganglionectomy, and also by labetalol, a nonselective β-blockade with α_1-blocking action. Thses observations suggest that not only β-adrenoceptors, but also α_1-adrenoceptors, play an important pathogenic role, especially under sympathetic stimulation, in LQTS. The clinical effects of α_1-blockade in congenital LQTS were investigated in 8 patients with familial or sporadic LQTS. Two measurements of the QT interval were taken, from the QRS onset to the T wave offset (QT) and from the QRS onset to the peak of the T wave (QTp). Using the Bruce protocol, an exercise test was performed after administration of β-blockade alone and again after administration of α_1-blockade. The following were compared:(1) Bazzet-corrected QT(QTc) and OTp(OTpc) intervals in the supine and standing position before exercise and in the early recovery phase after exercise;and (2) the slopes (reflecting the dynamic change in the QT interval during exercise) of the QT interval to heart rate were obtained from the linear regression during the exercise test. In the supine position before exercise, there was no change in the QTc before or after the addition of α_1-blockade (498±23 vs 486±23 ms[NS]). However, in the upright position before exercise and in the early recovery phase after exercise, QTc was significantly shortened from 523±21 to 483±22ms (p<0.01), and from 521±30 to 490±39ms (p<0.01), respectively, by α_1-blockade. The QTpc was unchanged in any situation. Consequently, QTc-QTpc was significantly shortened by α_1-blockade in the upright position before exercise and in the early recovery phase after exercise (131±36 to 105±37 ms (p<0.05), and 132±29 to 102±31 ms(p<0.01), respectively). The slopes of the QT interval-heart rate relation by linear regression became significantly steeper from -2.23±0.38 to -2.93±0.76(p<0.01) with the addition of α_1-blockade. The findings suggest that the addition of α_1-blockade attenuated the exercise-induced prolongation of the QT interval and that the rate adaptation of the QT interval to heart rate during exercise was improved. This indicates that additional treatment with α_1-blockade may be beneficial to prevent cardiac events in LQTS patients in whom ventricular arrhythmia is resistant to β-blockade.
社団法人日本循環器学会の論文
2001-06-20

Role of α_1-Blockade in Congenital Long QT Syndrome : Investigation by Exercise Stress Test

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