Not All Beta-Blockers Are Equal in the Management of Long QT Syndrome Types 1 and 2

Abstract

Objectives To compare the efficacy of beta-blockers (BB) in congenital long QT syndrome (LQTS). Background BB are the mainstay in managing LQTS. Studies comparing the efficacy of commonly-used BB are lacking and clinicians generally assume they are equally effective. Methods ECG and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n=134), metoprolol (n=147), and nadolol (n=101) were analyzed, excluding patients aged <1 year at BB initiation. Symptoms prior to therapy and the first breakthrough cardiac events (BCEs) were documented. Results Patients (56% females, 27% symptomatic, HR 76±16 bpm, QTc 472±46 ms) were started on BB therapy at a median age of 14 years (IQR 8–32 years). QTc-shortening with propranolol was significantly greater than with other BB in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n=101), 15 had BCEs (all syncopes). QTc-shortening was significantly less-pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of other two BB combined, after adjustment for genotype (OR 3.95, 95% CI 1.2–13.1, p=0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients on metoprolol compared to propranolol/nadolol. Conclusions Propranolol has a significantly better QTc-shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used in symptomatic LQT1 and LQT2 patients.

Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia

“…The only patient who died during follow-up was the one who was switched suddenly from nadolol to metoprolol, despite the evidence of high risk for arrhythmic recurrences with this specific β-blocker in long-QT syndrome. 25 LCSD was associated with major reductions both in the number of patients with MCEs and in the actual number of MCEs. The impact of LCSD is clearly evident by the internal control analysis ( Figure 5) in which each patient served as his/her own control that shows a 92% reduction in MCEs.…”

Cardiac Events During Competitive, Recreational, and Daily Activities in Children and Adolescents With Long QT Syndrome

“…Increasingly, evidence suggests those who are asymptomatic at diagnosis remain so once started on appropriate β‐blockers3, 20. The increasing recognition of LQTS in the medical community and the implementation of familial screening means that many are diagnosed prior to the onset of symptoms, compared with prior eras when more than half of patients were diagnosed following a symptomatic event 3, 18, 19, 21.…”

Genetic and Clinical Advances in Congenital Long QT Syndrome

“…77 In LQT1 and LQT2, propranolol (2-4 mg · kg -1 · day -1 ) and nadolol (1-1.5 mg · kg -1 · day -1 ) have been shown to be much more effective than metoprolol in suppressing recurrent cardiac events. 78 Therefore, metoprolol should probably not be prescribed in symptomatic LQTS patients. 78, 79 Atenolol, not included in the aforementioned study, appears to be less effective, according to a study performed in (only) 28 genotyped patients with a median follow-up of 46 months.…”