More pronounced ECG-changes with non-selective than cardio-selective beta-blockers in long-QT syndrome type 1

Abstract Background Beta-blockers are the first-line therapy for patients with long QT syndrome (LQTS), resulting in a significant reduction in mortality. Non-selective beta-blockers are superior to cardio-selective beta-blockers in preventing arrhythmic events. However, it is unclear how the therapeutic efficacy should be monitored. Frequently used parameters such as QTc do not always adequately reflect the arrhythmogenic risk. Previously, we have demonstrated that Tpeak/end - a marker for transmural heterogeneity - and delta Tpeak/end (V5-V2) are suitable risk predictors in LQT1, particularly after exercise. We therefore aimed to investigate the effect of beta-blockers on these electrical parameters. Methods In a cohort of 12 patients with genetically confirmed LQT1 (6 of them with a history of (pre)syncope or symptomatic ventricular tachycardia), we determined standard electrical parameters including heart rate corrected QT-interval (QTc) as well as markers for regional electrical heterogeneity such as Tpeak/end, at rest and during the recovery phase following an exercise stress test. The ECGs were evaluated before and at least several weeks after beta-blocker (BB) initiation. In addition, we investigated whether there were differences between cardioselective (sBB; n=10) and non-selective beta-blockers (nsBB; n=8). All patients had ECGs available for at least two categories analyzed (5 of them for each). Results At rest, we observed a non-significant trend towards QTc reduction, regardless of beta-blocker type [457±34ms noBB vs. 432±30ms with nsBB (p=0.1) and 432±27ms with sBB (p=0.1)]. Heart-rate corrected Tpeak/end tended to be lower in V2 with non-selective beta-blocker therapy [95±20ms noBB vs. 82±16ms with nsBB (p=0.1) and 82±12ms with sBB (p=0.2)] and was significantly reduced in V5 with non-selective beta-blocker therapy [95±13ms noBB vs. 81±15ms with nsBB (p=0.04) and 87±13ms with sBB (p=0.14)]. This effect was more pronounced after exercise, both in V2 [2min after exercise 115±26ms noBB vs. 91±19ms with nsBB, p=0.06; 4min after exercise 103±20ms noBB vs. 86±12ms with nsBB, p=0.006] and in V5 [2min after exercise 116±20ms noBB vs. 83±14ms with BB, p=0.0003; 4min after exercise 111±44ms noBB vs. 91±22ms with nsBB; p=0.1]. The effects were more pronounced in the asymptomatic cohort. In contrast, cardio-selective beta-blocker therapy showed no effect on Tpeak/end after exercise. QTc during exercise and delta Tpeak/end (V5-V2) were not altered by beta-blocker (nsBB and sBB) therapy. Conclusion The parameter Tpeak/end was significantly shortened with non-selective beta-blocker therapy, indicating a decreased electrical heterogeneity. The fact that Tpeak/end remained unchanged with cardio-selective beta-blocker therapy (known to be less effective in LQTS) suggests that this parameter could potentially be used to monitor therapeutic response to non-selective beta-blocker-therapy in LQT1. However, further evaluation is needed.