Electrical and Structural Insights into Right Ventricular Outflow Tract Arrhythmogenesis

The right ventricular outflow tract (RVOT) is the major origin of ventricular arrhythmias, including premature ventricular contractions, idiopathic ventricular arrhythmias, Brugada syndrome, torsade de pointes, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy. The RVOT has distinct developmental origins and cellular characteristics and a complex myocardial architecture with high shear wall stress, which may lead to its high vulnerability to arrhythmogenesis. RVOT myocytes are vulnerable to intracellular sodium and calcium overload due to calcium handling protein modulation, enhanced CaMKII activity, ryanodine receptor phosphorylation, and a higher cAMP level activated by predisposing factors or pathological conditions. A reduction in Cx43 and Scn5a expression may lead to electrical uncoupling in RVOT. The purpose of this review is to update the current understanding of the cellular and molecular mechanisms of RVOT arrhythmogenesis.

Automated summary

The right ventricular outflow tract (RVOT) is a major source of ventricular arrhythmias. Various cellular and molecular mechanisms, including calcium handling protein modulation, enhanced CaMKII activity, ryanodine receptor phosphorylation, and elevated cAMP levels, contribute to arrhythmogenesis in RVOT. Decreased expression of Cx43 and Scn5a may also lead to electrical uncoupling. This review aims to provide an updated understanding of these mechanisms.