Role of alpha 1-blockade in congenital long QT syndrome - Investigation byexercise stress test

Beta-blockade is widely reported to reduce the incidence of syncope in 75-8 0% of patients with congenital long QT syndrome (LQTS). However, despite fu ll-dose beta -blockade, 20-25% of patients continue to have syncopal episod es and remain at high risk for sudden cardiac death. In some patients refra ctory to beta -blockade, the recurrence of arrhythmias is successfully prev ented by left stellate ganglionectomy, and also by labetalol, a nonselectiv e beta -blockade with alpha1-blocking action. These observations suggest th at not only beta -adrenoceptors, but also alpha1-adrenoceptors, play an imp ortant pathogenic role, especially under sympathetic stimulation, in LQTS. The clinical effects of alpha1-blockade in congenital LQTS were investigate d 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 beta -blockade alone a nd again after administration of alpha1-blockade. The following were compar ed: (1) Bazzet-corrected QT (QTc) and QTp (QTpc) intervals in the supine an d standing position before exercise and in the early recovery phase after e xercise; and (2) the slopes (reflecting the dynamic change in the QT interv al 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 al pha1-blockade (498 +/- 23 vs 486 +/- 23 ms [NS]). However, in the upright p osition before exercise and in the early recovery phase after exercise, QTc was significantly shortened from 523 +/- 21 to 483 +/- 22 ms (p<0.01), and from 521<plus/minus>30 to 490 +/- 39 ms (p<0.01), respectively, by <alpha> 1-blockade. The QTpc was unchanged in any situation. Consequently, QTc-QTpc was significantly shortened by alpha1-blockade in the upright position bef ore exercise and in the early recovery phase after exercise (131 +/- 36 to 105 +/- 37 ms (p<0.05), and 132<plus/minus>29 to 102 +/- 31 ms (p<0.01), re spectively). The slopes of the QT interval-heart rate relation by linear re gression became significantly steeper from -2.23<plus/minus>0.38 to -2.93 /-0.76 (p<0.01) with the addition of <alpha>1-blockade. The findings sugges t that the addition of alpha1-blockade attenuated the exercise-induced prol ongation 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 alpha1-blockade may be beneficial to prevent cardiac events in LQTS patients in whom ventricular arrhythmia is resistant to beta -bloc kade.