Abstract 12229: Bundle Branch Reentrant Ventricular Tachycardia: Novel Genetic Mechanisms in a Life-Threatening Arrhythmia
Introduction: Bundle branch reentrant ventricular tachycardia (BBRVT) is a life-threatening ventricular arrhythmia occurring secondary to macroreentry within the His-Purkinje system. Although classically associated with dilated cardiomyopathy, BBRVT may also occur in the setting of isolated, unexplained conduction system disease.
Hypothesis: Idiopathic BBRVT may be secondary to genetic mutations associated with conduction system disease.
Methods & Results: We identified 6 cases of BBRVT associated with normal biventricular size and function from 6 centers across North America. Study participants were screened for mutations within pre-specified genes linked to cardiac conduction system disease. Putative culprit mutations were identified in 3 of 6 cases, including 2 in SCN5A (Ala1905Gly [novel] and c.4719C>T [splice site mutation]) and 1 in LMNA (Leu327Val [novel]). Biophysical analysis of mutant Ala1905Gly Nav1.5 channels in tsA201 cells revealed significantly reduced peak current density and positive shifts in the voltage-dependence of activation consistent with a loss-of-function. The SCN5A c.4719C>T splice-site mutation has previously been reported as disease causing in 3 cases of Brugada syndrome, while the novel LMNA Leu327Val mutation was associated with a classic laminopathy phenotype. Following catheter ablation, BBRVT was non-inducible in all cases and no clinical recurrences were observed during follow-up.
Conclusions: Our investigation into apparent idiopathic BBRVT has identified the first genetic culprits for this life-threatening ventricular arrhythmia. This provides further insight into its underlying pathophysiology and emphasizes that conduction system disease, in the absence of ventricular dilation, serves as a sufficient substrate for BBRVT. Our findings also highlight BBRVT as a novel genetic etiology of unexplained sudden cardiac death that can be cured with catheter ablation.
Author Disclosures: J.D. Roberts: None. M.H. Gollob: None. C. Young: None. S.P. Connors: None. C. Gray: None. S.B. Wilton: None. M.S. Green: None. D.W. Zhu: None. K.A. Hodgkinson: None. A. Poon: None. Q. Li: None. N. Orr: None. A.S. Tang: None. G.J. Klein: None. J. Wojciak: None. J. Campagna: None. J.E. Olgin: None. N. Badhwar: None. V. Vedantham: None. G. Marcus: None. P. Kwok: None. R.C. Deo: None. M.M. Scheinman: None.
- © 2016 by American Heart Association, Inc.