Gating-Dependent Mechanisms for Flecainide Action inSCN5A-Linked Arrhythmia Syndromes
Key result
Flecainide (1 micromol/L) tonic block was significantly higher in 1795insD (58.0%, P<0.01) and DeltaKPQ (39.4%, P<0.05) mutant channels compared to wild type (16.8%).
Population
tsA-201 cells transfected with DeltaKPQ, 1795insD, and wild type SCN5A
Comparison
Flecainide (1 micromol/L) vs Wild type channels
Design
Preclinical
Authors
Discussion
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Implication
Caution with flecainide in LQT3 due to Brugada-like changes; leaves open gating-specific Na-channel modulation as therapy.
Structured PICO
P
Population
In vitro study using tsA-201 cells transfected with SCN5A mutations (DeltaKPQ and 1795insD) to evaluate flecainide sensitivity.
I
Intervention
Flecainide (1 micromol/L)
C
Comparator
Wild type channels
O
Outcome
Whole-cell Na current (I(Na)) tonic block and recovery from inactivationsurrogate
Main Result
Absolute Event Rate: 58% vs 16.8%
p-value: p=<0.01
Specific SCN5A inactivation gating defects (closed-state fast inactivation and intermediate inactivation) explain the proarrhythmic sensitivity to flecainide in patients with LQT3 and Brugada syndrome.
Cite This Study
Viswanathan et al. (2001) studied LQT3 and Brugada syndrome. Flecainide vs. Wild type channels was evaluated on Tonic I(Na) block (p=<0.01). Flecainide (1 micromol/L) tonic block was significantly higher in 1795insD (58.0%, P<0.01) and DeltaKPQ (39.4%, P<0.05) mutant channels compared to wild type (16.8%).