Details

Autor(en) / Beteiligte

• Behr, Elijah R
• Ben-Haim, Yael
• Ackerman, Michael J
• Krahn, Andrew D
• Wilde, Arthur A M

Titel

Brugada syndrome and reduced right ventricular outflow tract conduction reserve: a final common pathway?

Ist Teil von

• European heart journal, 2021-03, Vol.42 (11), p.1073-1081

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2021

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Brugada syndrome (BrS) was first described as a primary electrical disorder predisposing to the risk of sudden cardiac death and characterized by right precordial lead ST elevation. Early description of right ventricular structural abnormalities and of right ventricular outflow tract (RVOT) conduction delay in BrS patients set the stage for the current controversy over the pathophysiology underlying the syndrome: channelopathy or cardiomyopathy; repolarization or depolarization. This review examines the current understanding of the BrS substrate, its genetic and non-genetic basis, theories of pathophysiology, and the clinical implications thereof. We propose that the final common pathway for BrS could be viewed as a disease of ‘reduced RVOT conduction reserve’. Graphical abstract Brugada syndrome (BrS) as a disease of impaired right ventricular outflow tract (RVOT) conduction reserve. Normally, intrinsic RVOT conduction reserve may be affected by a patient’s age and gender. In BrS, cellular and tissue abnormalities cause a reduction in RVOT conduction reserve: genetic abnormalities, whether mediated by a pathogenic SCN5A variant, an increased BrS-PRS, and/or additional genetic insults, may have direct effects on Nav1.5, as well as tissue effects causing RVOT inflammation, fibrosis, and gap junction abnormalities. Decreased Nav1.5 current, together with electrical discontinuity caused by RVOT structural changes, converges to disrupt normal depolarization, with or without secondary repolarization effects, leading to impairment of the conduction reserve of the RVOT. In this framework, the marginal conduction reserve can be exposed by acute modulators such as fever, drugs, and altered vagal tone which further impair conduction and expose the Brugada phenotype.