title: Autonomic control of heart rate and QT interval variability influences arrhythmic risk in long QT syndrome type 1.
abstract: BACKGROUND
  A puzzling feature of the long QT syndrome (LQTS) is that family members carrying the same mutation often have divergent symptoms and clinical outcomes.
  
  
  OBJECTIVE
  This study tested the hypothesis that vagal and sympathetic control, as assessed by spectral analysis of spontaneous beat-to-beat variability of RR and QT intervals from standard 24-h electrocardiogram Holter recordings, could modulate the severity of LQTS type 1 (LQT1) in 46 members of a South-African LQT1 founder population carrying the clinically severe KCNQ1 A341V mutation.
  
  
  METHODS
  Nonmutation carriers (NMCs) (n = 14) were compared with mutation carriers (MCs) (n = 32), 22 with and 10 without major symptoms. We assessed the effect of circadian rhythm and beta-blocker therapy over traditional time and frequency domain RR and QT variability indexes.
  
  
  RESULTS
  The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest.
  
  
  CONCLUSIONS
  The present data identified an additional factor contributing to the differential arrhythmic risk among patients with LQT1 carrying the same mutation. A healthy autonomic control confers a high risk, whereas patients with higher sympathetic control of the QT interval and reduced vagal control of heart rate are at lower risk. This differential "autonomic make-up," likely under genetic control, will allow refinement of risk stratification within families with LQTS, leading to more targeted management.
authors: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; IRCCS Galeazzi Orthopedic Institute, Milan, Italy. Electronic address: alberto.porta@unimi.it.
authors: Alberto
authors: A
authors: Porta
authors: Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors: Giulia
authors: G
authors: Girardengo
authors: Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy.
authors: Vlasta
authors: V
authors: Bari
authors: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee.
authors: Alfred L
authors: AL
authors: George
authors: Department of Internal Medicine, University of Stellenbosch, Stellenbosch, South Africa.
authors: Paul A
authors: PA
authors: Brink
authors: Department of Internal Medicine, University of Stellenbosch, Stellenbosch, South Africa.
authors: Althea
authors: A
authors: Goosen
authors: Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors: Lia
authors: L
authors: Crotti
authors: Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors: Peter J
authors: PJ
authors: Schwartz
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D016022:Case-Control Studies; D002940:Circadian Rhythm; D004562:Electrocardiography; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D029597:Romano-Ward Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014630:Vagus Nerve / Q000503:physiopathology*
chemical_list: D000319:Adrenergic beta-Antagonists; D051657:KCNQ1 Potassium Channel
keywords: QT variability; autonomic nervous system; beta-blocker therapy; cardiovascular control; heart rate variability
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