title: Syncope in genotype-negative long QT syndrome family members.
abstract: Unaffected long-QT syndrome family members (FMs) frequently experience syncope. The aims of this study were to test the hypothesis that syncope events in FMs are benign events and to compare clinical characteristics, triggers eliciting the syncope events, and long-term outcomes between FMs and those with LQT1 or LQT2 mutations from the international Long QT Syndrome Registry. A total of 679 FMs, 864 LQT1 patients, and 782 LQT2 patients were included. Seventy-eight FMs (11%) experienced cardiovascular events. Almost all cardiovascular events were nonfatal syncope; only 1 FM, with an additional mitral valve prolapse, experienced aborted cardiac arrest during exercise. The mean age at first syncope in FMs was 17 years, and female FMs experienced syncope more frequently than male FMs (14% vs 9%, p = 0.027). Syncope was more frequently triggered by exercise in LQT1 patients (43% in LQT1 patients vs 5% in FMs, p <0.001), while syncope triggered by a variety of other triggers was more frequent in FMs (54% in FMs vs 22% in LQT1 patients and 30% in LQT2 patients, p <0.001 for both). None of the FMs experienced aborted cardiac arrest or sudden cardiac death after the first syncopal episode. In conclusion, syncope is frequently present in FMs, and these syncopal events occurred more frequently in female than in male FMs, with an increased incidence in midadolescence. Triggers eliciting the syncopal events were different between FMs and patients with long-QT syndrome mutations. Hence, the type of trigger is useful in distinguishing between high- and low-risk syncope. These data indicate that FMs from families with LQTS have a benign form of syncope, most likely related to vasovagal syncope and not ventricular tachyarrhythmic syncope.
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Louise R A
authors.initials: LR
authors.lastname: Olde Nordkamp
authors.affiliation: Cardiology Division, University of Rochester Medical Centre, Rochester, New York.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.affiliation: Cardiology Division, University of Rochester Medical Centre, Rochester, New York.
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.affiliation: Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Wieling
authors.affiliation: Cardiology Division, University of Rochester Medical Centre, Rochester, New York.
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.affiliation: Cardiology Division, University of Rochester Medical Centre, Rochester, New York.
authors.forename: Bronislava
authors.initials: B
authors.lastname: Polonsky
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands. Electronic address: a.a.wilde@amc.uva.nl.
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.affiliation: Department of General Practice/Family Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Nynke
authors.initials: N
authors.lastname: van Dijk
authors.affiliation: Cardiology Division, University of Rochester Medical Centre, Rochester, New York.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013575:Syncope / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D004247:DNA