A comprehensive electrocardiographic, molecular, and echocardiographic study of Brugada syndrome: validation of the 2013 diagnostic criteria.
BACKGROUND
The debate on the diagnostic value of high intercostal spaces (ICSs) and of the number of diagnostic leads in Brugada syndrome (BrS) has been settled by a recent expert consensus statement.


OBJECTIVE
To test the validity, and the underlying anatomy, of the new electrocardiographic (ECG) diagnostic criteria using echocardiographic, molecular, and clinical evidence in 1 clinical study population with BrS.


METHODS
We analyzed 114 patients with BrS and with a spontaneous or drug-induced type 1 ECG pattern recorded in 1 or more right precordial leads in fourth, third, and second ICSs. The right ventricular outflow tract (RVOT) was localized by using echocardiography. All probands were screened on the SCN5A gene.


RESULTS
The percentage of mutation carriers (MCs) and the event rate were similar regardless of the diagnostic ICS (fourth vs high ICSs: MCs 23% vs 19%; event rate 22% vs 28%) and the number of diagnostic leads (1 vs ≥2: MCs 20% vs 22%; event rate 22% vs 27%). The concordance between RVOT anatomical location and the diagnostic ICSs was 86%. The percentage of the diagnostic ECG pattern recorded was significantly increased by the exploration of the ICSs showing RVOT by echocardiography (echocardiography-guided approach vs conventional approach 100% vs 43%; P < .001).


CONCLUSIONS
The high ICSs are not inferior to the standard fourth ICS for the ECG diagnosis of BrS, and the interindividual variability depends on the anatomical location of the RVOT as assessed by using echocardiography. This approach significantly increases diagnostic sensitivity without decreasing specificity and fully supports the recently published new diagnostic criteria.
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Simone
S
Savastano
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Roberto
R
Rordorf
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Alessandro
A
Vicentini
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Barbara
B
Petracci
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Erika
E
Taravelli
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Silvia
S
Castelletti
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Alessandra
A
D'Errico
Laboratory of Cardiovascular Genetics and Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Margherita
M
Torchio
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Cinzia
C
Dossena
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Paola
P
Novara
Laboratory of Cardiovascular Genetics and Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Federica
F
Dagradi
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Maurizio
M
Landolina
Laboratory of Cardiovascular Genetics and Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Carla
C
Spazzolini
Department of Molecular Medicine, University of Pavia, Pavia, Italy; Laboratory of Cardiovascular Genetics and Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Lia
L
Crotti
Laboratory of Cardiovascular Genetics and Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy. Electronic address: peter.schwartz@unipv.it.
Peter J
PJ
Schwartz
D000328:Adult; D053840:Brugada Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D004452:Echocardiography / Q000379:methods*; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
Brugada syndrome; Diagnostic criteria; Echocardiography; Electrocardiography; SCN5A