PMID- 22475738
OWN - NLM
STAT- MEDLINE
DCOM- 20121025
LR  - 20121115
IS  - 0870-2551 (Print)
IS  - 0870-2551 (Linking)
VI  - 31
IP  - 5
DP  - 2012 May
TI  - [Diagnostic criteria for the Brugada syndrome: can they be improved?].
PG  - 355-62
AB  - INTRODUCTION: Diagnosis of Brugada syndrome (BS) currently requires documentation 
      of a characteristic repolarization pattern (type 1 Brugada ECG). Mutations in the 
      SCN5A gene, which codes for sodium channel Na(v) 1.5, are found in 38% of 
      familial cases of BS. Sodium current dysfunction negatively affects the cardiac 
      fast response action potential, particularly in atrial and ventricular myocytes 
      and in the fast-conducting Purkinje system. OBJECTIVES: To detect carriers of 
      SCN5A mutations without using the characteristic repolarization pattern (type 1 
      Brugada ECG). METHODS: Of a total of 141 members of three different families 
      including 55 carriers of two nonsense SCN5A mutations causing BS, all those aged 
      over 16 (113 individuals, 42 carriers) were studied. The PR interval (PR) and QT 
      dispersion (QTd) between leads V1 and V3 were measured on conventional ECG. Using 
      signal-averaged ECG the total duration of the filtered QRS complex (fQRS), the 
      root-mean-square (RMS40) and the low-amplitude signal (LAS) were measured. The 
      following procedures were developed to detect carriers/To detect carriers the 
      following procedures were developed: (1) a screening test (ScreenTest) with PS 
      (PR+fQRS) > or = 250 (250ms is 80% of the theoretical maximum in healthy 
      individuals); and (2) a diagnostic test (DiagTest) for the simultaneous 
      fulfillment of four conditions: PS > or = 250 and QTd > or = 10 and LAS > 26 and 
      RMS40 < or = 29 (the latter two cut-offs are approximately 70% of the theoretical 
      maximum in healthy carriers). RESULTS: Significant differences in PR, QTd, QRSf, 
      RMS40 and LAS were found between carriers and non-carriers. The SCN5A gene was 
      associated with all these variables, the strongest association being with PR. 
      Both tests were applied to 63 family members (38 carriers). The ScreenTest was 
      positive in 38 of 38 carriers, with eight false positives in 27 non-carriers 
      (sensitivity [SE] = 100% and specificity [SP] = 66.67%). From ROC curve analysis 
      a cut-off of PS = 252.5 shows SE = 100% and SP = 76% and a cut-off of PS = 260 
      shows SE=94.7% and SP = 84%. The DiagTest was positive in 36 of 38 carriers, with 
      three false positives: SE = 94.74% and SP = 88.89%. From ROC curve analysis a 
      multivariate logistic model identifies a cut-off with SE = 92% and SP = 92%. In 
      the same group the SE and SP of the characteristic spontaneous repolarization 
      pattern (type 1 Brugada ECG) to detect carriers were 52.4% and 97.2%, 
      respectively, and the difference between the SE of the DiagTest and of the 
      typical repolarization pattern is statistically significant. CONCLUSIONS: The 
      ScreenTest and DiagTest are more effective tools than the characteristic 
      repolarization pattern to discriminate between carriers and non-carriers of these 
      two nonsense SCN5A mutations. We suggest their use in first-degree relatives of 
      Brugada patients when the results of genetic testing are not available, in a 
      score of disease probability in individuals with idiopathic Brugada ECG, and in 
      patients with arrhythmias or other Brugada-related symptoms presenting type 2 or 
      type 3 Brugada ECG.
FAU - Santos, Luis Ferreira
AU  - Santos LF
AD  - Servico de Cardiologia, Hospital Sao Teotonio, EPE Viseu, Viseu, Portugal. 
      luisferreirasantos@gmail.com
FAU - Pereira, Telmo
AU  - Pereira T
FAU - Rodrigues, Bruno
AU  - Rodrigues B
FAU - Correia, Emanuel
AU  - Correia E
FAU - Moreira, Davide
AU  - Moreira D
FAU - Nunes, Luis
AU  - Nunes L
FAU - Costa, Antonio
AU  - Costa A
FAU - Elvas, Luis
AU  - Elvas L
FAU - Machado, Jose Carlos
AU  - Machado JC
FAU - Castedo, Sergio
AU  - Castedo S
FAU - Henriques, Carla
AU  - Henriques C
FAU - Matos, Ana
AU  - Matos A
FAU - Santos, Oliveira
AU  - Santos O
LA  - por
PT  - English Abstract
PT  - Journal Article
TT  - Criterios de diagnostico da sindrome de Brugada. Podemos melhorar?
PL  - Portugal
TA  - Rev Port Cardiol
JT  - Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de 
      Cardiologia = Portuguese journal of cardiology : an official journal of the 
      Portuguese Society of Cardiology
JID - 8710716
RN  - 0 (NAV1.5 Voltage-Gated Sodium Channel)
RN  - 0 (SCN5A protein, human)
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Adult
MH  - Brugada Syndrome/*diagnosis/genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - NAV1.5 Voltage-Gated Sodium Channel
MH  - Sodium Channels/genetics
EDAT- 2012/04/06 06:00
MHDA- 2012/10/26 06:00
CRDT- 2012/04/06 06:00
PHST- 2011/01/07 00:00 [received]
PHST- 2011/09/22 00:00 [accepted]
PHST- 2012/04/06 06:00 [entrez]
PHST- 2012/04/06 06:00 [pubmed]
PHST- 2012/10/26 06:00 [medline]
AID - S0870-2551(12)00048-0 [pii]
AID - 10.1016/j.repc.2011.09.023 [doi]
PST - ppublish
SO  - Rev Port Cardiol. 2012 May;31(5):355-62. doi: 10.1016/j.repc.2011.09.023.