Abstract:
BACKGROUND:The right ventricular outflow tract (RVOT) is acknowledged to be responsible for arrhythmogenesis in Brugada syndrome (BrS), but the pathophysiology remains controversial. OBJECTIVES:This study assessed the substrate underlying BrS at post-mortem and in vivo, and the role for open thoracotomy ablation. METHODS:Six whole hearts from male post-mortem cases of unexplained sudden death (mean age 23.2 years) with negative specialist cardiac autopsy and familial BrS were used and matched to 6 homograft control hearts by sex and age (within 3 years) by random risk set sampling. Cardiac autopsy sections from cases and control hearts were stained with picrosirius red for collagen. The RVOT was evaluated in detail, including immunofluorescent stain for connexin-43 (Cx43). Collagen and Cx43 were quantified digitally and compared. An in vivo study was undertaken on 6 consecutive BrS patients (mean age 39.8 years, all men) during epicardial RVOT ablation for arrhythmia via thoracotomy. Abnormal late and fractionated potentials indicative of slowed conduction were identified, and biopsies were taken before ablation. RESULTS:Collagen was increased in BrS autopsy cases compared with control hearts (odds ratio [OR]: 1.42; p = 0.026). Fibrosis was greatest in the RVOT (OR: 1.98; p = 0.003) and the epicardium (OR: 2.00; p = 0.001). The Cx43 signal was reduced in BrS RVOT (OR: 0.59; p = 0.001). Autopsy and in vivo RVOT samples identified epicardial and interstitial fibrosis. This was collocated with abnormal potentials in vivo that, when ablated, abolished the type 1 Brugada electrocardiogram without ventricular arrhythmia over 24.6 ± 9.7 months. CONCLUSIONS:BrS is associated with epicardial surface and interstitial fibrosis and reduced gap junction expression in the RVOT. This collocates to abnormal potentials, and their ablation abolishes the BrS phenotype and life-threatening arrhythmias. BrS is also associated with increased collagen throughout the heart. Abnormal myocardial structure and conduction are therefore responsible for BrS.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Nademanee K,Raju H,de Noronha SV,Papadakis M,Robinson L,Rothery S,Makita N,Kowase S,Boonmee N,Vitayakritsirikul V,Ratanarapee S,Sharma S,van der Wal AC,Christiansen M,Tan HL,Wilde AA,Nogami A,Sheppard MN,Veerakul G,doi
10.1016/j.jacc.2015.08.862subject
Has Abstractpub_date
2015-11-03 00:00:00pages
1976-1986issue
18eissn
0735-1097issn
1558-3597pii
S0735-1097(15)05916-1journal_volume
66pub_type
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