title: The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands.
abstract: OBJECTIVE
  Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmic disorder with a highly malignant clinical course. Exercise-stress test is the first-line approach to diagnose suspected individuals. We sought to elucidate the value of exercise-stress test for predicting mutations and future cardiac events in CPVT-family relatives.
  
  
  RESULTS
  The present study included 67 asymptomatic relatives (24 ± 15 years) of 17 genetically positive CPVT probands, who underwent exercise-stress test without any medication and genetic testing. Exercise-stress test, which was considered positive with the induction of ventricular tachycardia or premature ventricular contractions consisting of bigeminy or couplets, was positive in 17 relatives (25%). Genetic analysis disclosed mutations in 16 of these 17 relatives (94%) and in 16 of the 50 relatives (32%) with negative exercise-stress test; the sensitivity and specificity for a positive genotype were 50 and 97%, respectively (P< 0.001). Among 32 mutation carriers, cardiac events occurred in 7 of the 16 relatives with positive and 2 of the 16 relatives with negative exercise-stress test during the follow-up period of 9.6 ± 3.8 years, and four with positive and two with negative stress test were not on regular beta-blocker treatment at these events. In the 16 relatives with positive stress test, those on beta-blocker treatment demonstrated a trend of lower cardiac event rate (Log-rank P= 0.054).
  
  
  CONCLUSIONS
  In asymptomatic relatives of CPVT probands, exercise-stress test can be used as a simple diagnostic tool. Nevertheless, because of the low sensitivity for predicting mutations and future cardiac events in those with negative stress test, genetic analysis should be performed to improve patient management.
authors.affiliation: Service de Cardiologie,  Hôpital Bichat, Assistance Publique - Hôpitaux de Paris,  Université Paris Diderot, INSERM U942, 46, rue Henri Huchard 75877 Paris Cedex 18, Paris,  France.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Hayashi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denjoy
authors.forename: Meiso
authors.initials: M
authors.lastname: Hayashi
authors.forename: Fabrice
authors.initials: F
authors.lastname: Extramiana
authors.forename: Alice
authors.initials: A
authors.lastname: Maltret
authors.forename: Nathalie
authors.initials: N
authors.lastname: Roux-Buisson
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lupoglazoff
authors.forename: Didier
authors.initials: D
authors.lastname: Klug
authors.forename: Philippe
authors.initials: P
authors.lastname: Maury
authors.forename: Anne
authors.initials: A
authors.lastname: Messali
authors.forename: Pascale
authors.initials: P
authors.lastname: Guicheney
authors.forename: Antoine
authors.initials: A
authors.lastname: Leenhardt
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D002648:Child; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D004562:Electrocardiography; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D013575:Syncope / Q000188:drug therapy / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000235:genetics*; D018879:Ventricular Premature Complexes / Q000188:drug therapy / Q000235:genetics; D055815:Young Adult; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D000319:Adrenergic beta-Antagonists