| Autor: |
Jason D, Roberts, Michael H, Gollob, Charlie, Young, Sean P, Connors, Chris, Gray, Stephen B, Wilton, Martin S, Green, Dennis W, Zhu, Kathleen A, Hodgkinson, Annie, Poon, Qiuju, Li, Nathan, Orr, Anthony S, Tang, George J, Klein, Julianne, Wojciak, Joan, Campagna, Jeffrey E, Olgin, Nitish, Badhwar, Vasanth, Vedantham, Gregory M, Marcus, Pui-Yan, Kwok, Rahul C, Deo, Melvin M, Scheinman |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
JACC. Clinical electrophysiology. 3(3) |
| ISSN: |
2405-5018 |
| Popis: |
This study sought to investigate for an underlying genetic etiology in cases of apparent idiopathic bundle branch re-entrant ventricular tachycardia (BBRVT).BBRVT is a life-threatening arrhythmia occurring secondary to macro-re-entry within the His-Purkinje system. Although classically associated with dilated cardiomyopathy, BBRVT may also occur in the setting of isolated, unexplained conduction system disease.Cases of BBRVT with normal biventricular size and function were recruited from 6 North American centers. Enrollment required a clinically documented wide complex tachycardia and BBRVT proven during invasive electrophysiology study. Study participants were screened for mutations within genes associated with cardiac conduction system disease. Pathogenicity of identified mutations was evaluated using in silico phylogenetic and physicochemical analyses and in vitro biophysical studies.Among 6 cases of idiopathic BBRVT, each presented with hemodynamic compromise and 2 suffered cardiac arrests requiring resuscitation. Putative culprit mutations were identified in 3 of 6 cases, including 2 in SCN5A (Ala1905Gly [novel] and c.4719CT [splice site mutation]) and 1 in LMNA (Leu327Val [novel]). Biophysical analysis of mutant Ala1905Gly NaOur investigation into apparent idiopathic BBRVT has identified the first genetic culprits for this life-threatening arrhythmia, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing in this condition. Our findings also highlight BBRVT as a novel genetic etiology of unexplained sudden cardiac death that can be cured with catheter ablation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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