title: Beta-blocker therapy failures in symptomatic probands with genotyped long-QT syndrome.
abstract: Beta-blocker therapy is one of the principal therapies for congenital long-QT syndrome (LQTS). However, breakthrough cardiac events occur while being treated with beta-blockers. We sought to determine the frequency of and clinical correlates underlying beta-blocker therapy failures in genotyped, symptomatic LQTS probands. The medical records were analyzed only for genotyped LQTS probands who presented with a LQTS-attributable clinical event and were receiving beta-blocker therapy. The study cohort comprised 28 such patients: 18 KCNQ1/KVLQT1(LQT1), 7 KCNH2/HERG (LQT2), and 3 SCN5A (LQT3). The prescribed beta-blocker was atenolol (12), propranolol (10), metoprolol (4), and nadolol (2). Beta-blocker therapy failure was defined as breakthrough cardiac events including syncope, aborted cardiac arrest (ACA), appropriate implantable cardioverter-defibrillator (ICD) therapy, or sudden death occurring while on beta-blocker therapy. During a median follow-up of 46 months, 7/28 (25%) LQTS probands experienced a total of 15 breakthrough cardiac events. Their initial presentation was ACA (3), bradycardia during infancy (2), and syncope (2). The underlying genotype was KVLQT1 (6) and HERG (1). Two breakthroughs were attributed to noncompliance. Of the 13 breakthroughs occurring while compliant, 10 occurred with atenolol and 3 with propranolol (p = 0.03). In this study cohort, one-fourth of genotyped LQTS probands failed beta-blocker therapy. Treatment with atenolol, young age at diagnosis, initial presentation with ACA, KVLQT1 genotype, and noncompliance may be important factors underlying beta-blocker therapy failures.
authors.affiliation: Department of Pediatric and Adolescent Medicine/Division of Pediatric Cardiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chatrath
authors.forename: C M
authors.initials: CM
authors.lastname: Bell
authors.forename: M J
authors.initials: MJ
authors.lastname: Ackerman
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005838:Genotype; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010349:Patient Compliance; D024642:Potassium Channels, Voltage-Gated; D011433:Propranolol / Q000627:therapeutic use; D012189:Retrospective Studies; D015222:Sodium Channels; D017211:Treatment Failure
chemical_list: D000319:Adrenergic beta-Antagonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels; D001262:Atenolol; D011433:Propranolol