The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands

• Published in: Europace (London, England) England), 2012-09, Vol.14 (9), p.1344-1351
• Main Authors: Hayashi, Miyuki, Denjoy, Isabelle, Hayashi, Meiso, Extramiana, Fabrice, Maltret, Alice, Roux-Buisson, Nathalie, Lupoglazoff, Jean-Marc, Klug, Didier, Maury, Philippe, Messali, Anne, Guicheney, Pascale, Leenhardt, Antoine
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenergic beta-Antagonists; Adrenergic beta-Antagonists - therapeutic use; Adult; Cardiology and cardiovascular system; Child; Death, Sudden, Cardiac; Death, Sudden, Cardiac - prevention & control; Electrocardiography; Exercise Test; Exercise Test - methods; Female; Genetic analysis; Heart Rate; Heart Rate - drug effects; Heart Rate - genetics; Human health and pathology; Humans; Life Sciences; Male; Mutation; Syncope; Syncope - drug therapy; Syncope - genetics; Tachycardia, Ventricular; Tachycardia, Ventricular - drug therapy; Tachycardia, Ventricular - genetics; Ventricular Premature Complexes; Ventricular Premature Complexes - drug therapy; Ventricular Premature Complexes - genetics; Young Adult
• ISSN: 1099-5129; 1532-2092
• DOI: 10.1093/europace/eus031

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. 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). 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.