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 John Ackerman

Research output: Contribution to journalArticle

7 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(dot operator)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)
JournalHeart Rhythm
StateAccepted/In press - 2017


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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Lidocaine attenuation testing: An in vivo investigation of putative LQT3-associated variants in the SCN5A-encoded sodium channel'. Together they form a unique fingerprint.

  • Cite this