[ARVD-FORUM] ARVD and Brugada Syndrome. Dr. Perez Riera
ARVD Symposium
info at arvd-symposium.org
Tue Apr 12 22:22:30 ART 2005
English - Portuguese
In 1996, Corrado et al (Corrado D, Nava A, Buja G, et al. Familial
cardiomyopathy underlies syndrome of right bundle branch block, ST segment
elevation and sudden death. J Am Coll Cardiol 1996, 27: 443-448) presented
data in support of the hypothesis that a subpopulation of patients with
ARVC/D, referred to as "concealed forms," present with the typical clinical
and electrocardiographic features of the Brugada syndrome (BrS), including
the presence of type 1 ST segment elevation and polymorphic ventricular
tachycardia (PVT).
The only gene thus far linked to BrS is SCN5A, the gene that encodes the alpha
subunit of the cardiac sodium channel, which is named today BrS1 or first
BrS. The cardiac sodium channel isoform encodes hH1 and has been mapped to
the short arm of chromosome 3 p21-24 loci (Chen Q, Kirsch GE, Zhang D,
Brugada R, Brugada P, Brugada J, et al. Genetic basis and molecular
mechanisms for idiopathic ventricular fibrillation. Nature 1998;
392:293-296). A second more benign form, known as BrS2, was mapped to
chromosome 3p22-25. This variant was reported by Weiss et al (Weiss R,
Barmada MM, Nguyen T, et al. Clinical and molecular heterogeneity in the
Brugada syndrome: a novel gene locus on chromosome 3.Circulation. 2002;
105:707-713) in a single large family. A BrS locus distinct from SCN5A is
associated with progressive conduction disease, a low sensitivity to
procainamide testing, and a relatively good prognosis. Screening of several
candidates in the region (including two sodium channels, SCN510A and SCN512A)
failed to identify the causal gene.
ARVC/D Type 5: the affected locus was mapped to chromosome 3. The locus is
3p21.3.3p23 and 3p25 deoxyribonucleic acid (DNA) haplotype at locus ARVD5 but
different from Brugada Syndrome (BrS). Autosomal Dominant pattern of
Inheritance. Cytogenetics is 3p23 A peak 2-point lod score of 6.91, which
was obtained with marker D3S3613 at a recombination fraction of 0.0.
Haplotype analysis identified a shared region of 9.3 cM between markers
D3S3610 and D3S3659. The gene symbols are ARVC5 or ARVD5 (Ahmad F, Li D,
Karibe A, Gonzalez O, et al. Localization of a gene responsible for
arrhythmogenic right ventricular dysplasia to chromosome 3p23. Circulation.
1998;98: 2791-2795.). On the other hand, in the BrS the cardiac sodium
channel isoform encodes hH1 and has been mapped to the short arm of
chromosome 3 p21-24 loci.(Cheng Q, Kirsch GE, Zhang D, et al. Genetic basis
and molecular mechanisms for idiopathic ventricular fibrillation. Nature.
1998; 392:293-296).
Furthermore, the risk of SCD is probably variable among different types of
ARVC/D. In Newfoundland, Canada, ARVD5 was reported to cause SCD in 44% of
affected males, while females had a more benign course with no SCD. It is
coincident with BrS (Dicks E, Hodgkinson K, Conners S. Initial clinical
manifestations of arrhythmogenic right ventricular cardiomyopathy. Am J Hum
Gen 2000; 67: 114a.).
The unknown mutation at the ARVD5 locus causing ARVC/D results in high
mortality. Risk stratification using genetic haplotyping and ICD therapy
produced improved survival for males. In the high risk group, 50% of males
were dead by 39 years and females by 71 years: relative risk of death was 5.1
(95% confidence interval 3 to 8.5) for males. The five-year mortality rate
after ICD in males was zero compared with 28% in control subjects (p =
0.009). Within five years, the ICD fired for VT in 70% and for VT >240
beats/min in 30%, with no difference in discharge rate when analyzed by ICD
indication. (Hodgkinson KA, Parfrey PS, Bassett AS, Kupprion C, Drenckhahn J,
Norman MW, et al. The impact of implantable cardioverter-defibrillator
therapy on survival in autosomal-dominant arrhythmogenic right ventricular
cardiomyopathy (ARVD5). J Am Coll Cardiol. 2005; 45:400-408.).
I think _different of others- , that the complications of Endomyocardial
Biopsy are insignificant, and because of its important benefit for an
accurate diagnosis, the procedure is recommend for differential diagnosis
between both entities and it would mean an end in the speculations.(Benedek
I, Hintea T.Endomyocardial biopsy in diagnosis of myocardial diseases.Rom J
Intern Med. 1999;37:207-215.)
Best regard
Andrés Ricardo Pérez Riera
---------------------------------------------------------------------------------------------------
Portugués
Em 1996, Corrado y col (Corrado D, Nava A, Buja G, et al. Familial
cardiomyopathy underlies syndrome of right bundle branch block, ST segment
elevation and sudden death. J Am Coll Cardiol 1996, 27: 443-448) aprestaram
dados mostrando que existia uma sub-população de pacientes portadores da DAVD
chamadas "formas ocultas" que se apresentavam com as características clínicas
típicas da syndrome de Brugada incluído o padrão tipo 1 eletrocardiográfico e
taquicardia ventricular polimórfica.
O único gene identificado na SBr é o SCN5A o qual codifica a sub-unidade alfa
do canal de sódio e se chama hoje SBr1 ou SBr primeiro. A isoforma do canal
de sódio codifica hH1 ha sido mapeada no braço curto do cromossomo 3p21-24
(Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada P, Brugada J, et al. Genetic
basis and molecular mechanisms for idiopathic ventricular fibrillation.
Nature 1998; 392:293-296). Uma forma mais benigna conhecida como SBr2, foi
mapeada no cromossomo 3p22-25. Este variante fora reportada por Weiss e col.
Numa única família numerosa. (Weiss R, Barmada MM, Nguyen T, et al. Clinical
and molecular heterogeneity in the Brugada syndrome: a novel gene locus on
chromosome 3. Circulation. 2002; 105:707-713) Esta forma BrS2 com locus
diferente do SCN5A se associa a doença de condução progressiva, baixa
sensibilidade ao tese de procainamida e possui relativamente bom prognóstico.
Rastreamento em vários candidates na região incluindo dos canais de sódio
SCN510A e SCN512A não conseguiram identificar o gene causal.
Na DAVC/D tipo 5 o lócus afetado tem sido mapeado no cromossomo 3 locus
3p21.3.3p23 e 3p 25 no DNA haloptipo porém, diferente da SBr A herença é
autossômica dominante, a citogenetica é 3p23 Um pico2-punto lod escore de
6.91, o qual fora obtido com marcador D3S313 na fração recombinante 0,0. A
análise do Halotipo identificou uma região compartilhada de 9.3 entre os
marcadores DeS3610 e D3S3659. O símbolo do gene é ARVC5 ou ARVD5 (Ahmad F, Li
D, Karibe A, Gonzalez O, et al. Localization of a gene responsible for
arrhythmogenic right ventricular dysplasia to chromosome 3p23. Circulation.
1998;98: 2791-2795.). Pelo contrário, na SBr a isoforma hH1 do canal de sódio
ha sido mapeada no braço curto do cromossomo 3p21-24 locus. (Cheng Q, Kirsch
GE, Zhang D, et al. Genetic basis and molecular mechanisms for idiopathic
ventricular fibrillation. Nature. 1998; 392:293-296).
Além disso, o risco de SCD é provavelmente variável entre tipos diferentes de
DAVD. Em Newfoudland Canadá A DAVD tipo 5 há sido reportada causando MCS em
44% dos homens, ao passo que nas mulheres apresentam uma evolução mais
benigna sem MCS fato coicidente com a SBr (Dicks E, Hodgkinson K, Conners S.
Initial clinical manifestations of arrhythmogenic right ventricular
cardiomyopathy. Am J Hum Gen 2000; 67: 114a.).
Uma mutação desconhecida do tipo DAVD5 resulta em elevada taxa de mortalidade.
A estratificação do risco utilizando a halotipificação e terapia com ICD
ocasionou grande melhor do prognóstico no sexo masculino. No grupo de alto
risco 50% dos homens faleceram aos 39 anos e as mulheres a os 71 anos. O
risco relativo de morte foi de 5.1 (95% de intervalo de confidência e a 8.5)
para homens. A taxa de mortalidade apos o implante do ICD aos 5 anos foi de
zero comparado com 28% nos controles ( p =0.009) . Dentro de 5 anos, o ICD
ateado fogo para TV em 70% e para TV 240 b/min em 30%, com nenhuma diferença
na taxa da descarga quando analisado pela indicação de ICD. Hodgkinson KA,
Parfrey PS, Bassett AS, Kupprion C, Drenckhahn J, Norman MW, et al. The
impact of implantable cardioverter-defibrillator therapy on survival in
autosomal-dominant arrhythmogenic right ventricular cardiomyopathy (ARVD5). J
Am Coll Cardiol. 2005; 45:400-408.).
Eu penso que a complicações da biopsia endomiocárdica são insignificante
diferentemente de outros e porque este daria um beneficio importante para um
diagnóstico apurado o procedimento é recomendado para o diagnóstico
diferencial e determinação a existência ou não de um link entre ambas
entidades..(Benedek I, Hintea T.Endomyocardial biopsy in diagnosis of
myocardial diseases.Rom J Intern Med. 1999;37:207-215.)
Grato
Andrés Ricardo Pérez Riera
--
Dr. Sergio Dubner
Director
Dr. Edgardo Schapachnik
Director
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