Lidocaine attenuation testing: An in vivo investigation of putative LQT3-associated variants in the SCN5A-encoded sodium channel

Heather N. Anderson, J. Martijn Bos, Jamie D. Kapplinger, Jana M. Meskill, Dan Ye, Michael J. Ackerman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background Long QT syndrome type 3 (LQT3) accounts for 5%–10% of long QT syndrome and results from gain-of-function mutations in the SCN5A-encoded sodium channel. Approximately 2% of healthy individuals host rare SCN5A variants of uncertain significance (VUS). Distinction of true LQT3-causative mutations from background genetic noise is essential. Objective The purpose of this study was to assess the use of the lidocaine attenuation test (LAT) in evaluating patients with possible LQT3. Methods We reviewed the LAT results and medical records for 25 patients with a possible LQT3-associated SCN5A variant. The LAT involved a loading dose of 1 mg/kg of intravenous lidocaine followed by continuous infusion at 50 μg/(kg⋅min) for 20 minutes. If the corrected QT interval shortened by ≥30 ms, the LAT was defined as positive. Results Sixteen patients (64%) had a positive LAT, 6 of which demonstrated the E1784K variant. A positive LAT correlated in 86% of cases with abnormal in vitro channel function (mean corrected QT interval attenuation 43 ± 3 ms vs 25 ± 5 ms for wild-type variants; P =.03). Four of 5 patients (80%) with a VUS had a positive LAT (T1304M [2 patients], L1786P, and R800L). The T1304M variant demonstrated abnormal in vitro function and a positive LAT, opening the door for a potential variant promotion from VUS to likely pathogenic. Conclusion The LAT may help distinguish true LQT3-causative mutations from an otherwise noncontributory VUS. Given that lidocaine acts as a late sodium current blocker, a positive LAT may enable the early identification of a pathological accentuation of the late sodium current that could be targeted therapeutically.

Original languageEnglish (US)
Pages (from-to)1173-1179
Number of pages7
JournalHeart rhythm
Issue number8
StatePublished - Aug 2017


  • Lidocaine attenuation test
  • Long QT syndrome
  • Long QT syndrome type 3
  • SCN5A
  • VUS

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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