title: Systematic ajmaline challenge in patients with long QT 3 syndrome caused by the most common mutation: a multicentre study.
abstract: OBJECTIVE
  Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K.
  
  
  RESULTS
  Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study. Besides routine clinical work-up, ajmaline challenge was performed after informed consent. A total of 23 subjects (11 female, mean age 27 ± 14 years) from 4 unrelated families with a family history of sudden cardiac death and familial diagnosis of the SCN5A-E1784K mutation underwent ajmaline challenge and genetic testing. Sixteen subjects (9 female) were found to be heterozygous carriers of SCN5A-E1784K. Ajmaline challenge was positive in 12 out of the 16 (75%) mutation carriers, but negative in all non-carriers. Following ajmaline, a significant shortening of the rate-corrected JT (JTc) interval was observed in mutation carriers. The baseline JTc interval was significantly longer in mutation carriers with a positive ajmaline challenge compared with those with a negative one.
  
  
  CONCLUSIONS
  Overlap of LQT3 and BrS in patients carrying the most common mutation is high. Therefore, ajmaline challenge represents an important step to rule out potential BrS overlap in these patients before starting sodium channel blockers for the beneficial effect of QT shortening in LQT3.
authors.affiliation: Department of Cardiology and Angiology, Rhythmology and Electrophysiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hohmann
authors.affiliation: 1st Department of Medicine-Cardiology, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Mannheim, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Rudic
authors.affiliation: Center of Cardiology, Clinic of Cardiology II/Electrophysiology, Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Konrad
authors.affiliation: Department of Cardiology and Angiology, Rhythmology and Electrophysiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Duncker
authors.affiliation: Department of Cardiology and Angiology, Rhythmology and Electrophysiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Thorben
authors.initials: T
authors.lastname: König
authors.affiliation: 1st Department of Medicine-Cardiology, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Mannheim, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany.
authors.forename: Erol
authors.initials: E
authors.lastname: Tülümen
authors.affiliation: Center of Cardiology, Clinic of Cardiology II/Electrophysiology, Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rostock
authors.affiliation: 1st Department of Medicine-Cardiology, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Mannheim, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.affiliation: Department of Cardiology and Angiology, Rhythmology and Electrophysiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Veltmann
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000404:Ajmaline / Q000008:administration & dosage*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000187:drug effects* / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D062606:Tertiary Care Centers; D013997:Time Factors; D061567:Voltage-Gated Sodium Channel Blockers / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000889:Anti-Arrhythmia Agents; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D061567:Voltage-Gated Sodium Channel Blockers; D000404:Ajmaline
keywords: Ajmaline; Brugada syndrome; Long QT syndrome; Overlap syndrome; Sodium channel blocker challenge