The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge.
BACKGROUND
Defects of the SCN5A gene encoding the cardiac sodium channel are associated with both the LQT3 subtype of long-QT syndrome and Brugada syndrome (BS). The typical manifestations of long-QT syndrome (QT interval prolongation) and BS (ST segment elevation in leads V1 through V3) may coexist in the same patients, which raises questions about the actual differences between LQT3 and BS. Intravenous flecainide is the standard provocative test used to unmask BS in individuals with concealed forms of the disease, and oral flecainide has been proposed as a treatment option for LQT3 patients because it may shorten their QT interval.


RESULTS
We tested the possibility that in some LQT3 patients, flecainide might not only shorten the QT interval, but also produce an elevation of the ST segment. A total of 13 patients from 7 LQT3 families received intravenous flecainide using the protocol used for BS. As expected, QT, QTc, JT, and JTc interval shortening was observed in 12 of the 13 patients, and concomitant ST segment elevation in leads V1 through V3 (>/=2 mm) was observed in 6 of the 13.


CONCLUSIONS
The data demonstrate that flecainide may induce ST segment elevation in LQT3 patients, raising concerns about the safety of flecainide therapy and demonstrating the existence of an intriguing overlap between LQT3 and BS.
Priori
S G
SG
Department of Molecular Cardiology, Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy. spriori@fsm.it
Napolitano
C
C
Schwartz
P J
PJ
Bloise
R
R
Crotti
L
L
Ronchetti
E
E
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000075202:Contraindications; D003937:Diagnosis, Differential; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005424:Flecainide / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009154:Mutation; D010641:Phenotype; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics
D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D005424:Flecainide