title: Ventricular dysfunction in a family with long QT syndrome type 3.
abstract: OBJECTIVE
  Long QT syndrome (LQTS) type 3 is characterized by prolonged ventricular repolarization due to persistent sodium inward current secondary to a mutation in SCN5a, the gene encoding for the α-subunit of the sodium channel. We speculated that by disrupting calcium homeostasis the persistent inward sodium current in patients with LQTS type 3 might cause derangement of diastolic function. We aimed to identify functional myocardial alterations in a family with a sodium channelopathy with a phenotype of both LQTS type 3 and Brugada syndrome.
  
  
  RESULTS
  The study group comprised 12 SCN5a mutation carriers (SCN5a-1795insD), 9 females and 3 males, mean age 35.7 ± 7.3 years, and 12 healthy controls. In addition to conventional echocardiographic measurements, two-dimensional speckle tracking was performed to assess tissue properties. Mean e' was lower in the patients compared with the controls (5.6 ± 0.75 vs. 6.7 ± 0.98 cm/s, P = 0.006). Onset QRS to maximum s' was longer in the patients than in the controls (0.20 ± 0.04 vs. 0.15 ± 0.05 s, P = 0.007), and the number of segments with post-systolic shortening was higher (6.58 ± 2.54 vs. 1.83 ± 1.64, P < 0.001).
  
  
  CONCLUSIONS
  Patients in this family with LQTS type 3 showed post-systolic shortening, as well as both left and right ventricular diastolic dysfunction. The underlying mechanism remains to be elucidated but the persistent sodium inward current leading to calcium overload might play a role, in particular regarding diastolic dysfunction.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Yoran M
authors.initials: YM
authors.lastname: Hummel
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Silvia
authors.initials: S
authors.lastname: Bugatti
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003971:Diastole; D018618:Echocardiography, Doppler, Color; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: Echocardiography; Long QT syndrome; Persistent inward current; Post-systolic shortening; SCN5a; Sodium channel; Speckle tracking