Systematic ajmaline challenge in patients with long QT 3 syndrome caused by the most common mutation: a multicentre study.
Aims
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.


Methods and 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.


Conclusion
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.
['Hohmann|Stephan|S|', 'Rudic|Boris|B|', 'Konrad|Torsten|T|', 'Duncker|David|D|', 'König|Thorben|T|', 'Tülümen|Erol|E|', 'Rostock|Thomas|T|', 'Borggrefe|Martin|M|', 'Veltmann|Christian|C|']
D000200:Action Potentials D000293:Adolescent D000328:Adult D000404:Ajmaline D000889:Anti-Arrhythmia Agents D053840:Brugada Syndrome D004252:DNA Mutational Analysis D003937:Diagnosis, Differential D004562:Electrocardiography D005260:Female D020022:Genetic Predisposition to Disease D005858:Germany D006339:Heart Rate D006801:Humans D008133:Long QT Syndrome D008297:Male D008875:Middle Aged D009154:Mutation D062554:NAV1.5 Voltage-Gated Sodium Channel D010641:Phenotype D011237:Predictive Value of Tests D062606:Tertiary Care Centers D013997:Time Factors D061567:Voltage-Gated Sodium Channel Blockers D055815:Young Adult
Ajmaline Overlap syndrome Brugada syndrome Long QT syndrome Sodium channel blocker challenge