Format

Send to

Choose Destination
See comment in PubMed Commons below
J Cardiovasc Electrophysiol. 2013 Sep;24(9):1015-20. doi: 10.1111/jce.12172. Epub 2013 May 20.

Mutation location effect on severity of phenotype during exercise testing in type 1 long-QT syndrome: impact of transmembrane and C-loop location.

Author information

1
University of Western Ontario, London, Ontario, Canada.

Abstract

BACKGROUND:

Targeted mutation site-specific differences have correlated C-loop missense mutations with worse outcomes and increased benefit of beta-blockers in LQT1. This observation has implicated the C-loop region as being mechanistically important in the altered response to sympathetic stimulation known to put patients with LQT1 at risk of syncope and sudden cardiac death.

OBJECTIVE:

The objective of this study was to determine if there is mutation site-specific response to sympathetic stimulation and beta-blockers using exercise testing.

METHODS:

This study is a retrospective review of LQT1 patients undergoing exercise testing at 3 academic referral centers.

RESULTS:

A total of 123 patients (age 28 ± 17 years, 59 male) were studied including 34 patients (28%) with C-loop mutations. There were no significant differences in supine, standing, peak exercise and 1-minute recovery QTc duration between patients with C-loop mutations and patients with alternate mutation sites. In 37 patients that underwent testing on and off beta-blockers, beta-blocker use was associated with a significant reduction in supine, standing and peak exercise QTc. This difference was not seen in the small group of patients (7/37) with C-loop mutations. There was no difference in QTc at 1 and 4 minutes into recovery.

CONCLUSIONS:

Genetically confirmed LQT1 patients in this study cohort with C-loop mutations did not demonstrate the expected increase in QTc in response to exercise, or resultant response to beta-blocker. The apparent increased risk of cardiac events associated with C-loop mutation sites and the marked benefit received from beta-blocker therapy are not reflected by exercise-mediated effects on QTc in this study population.

KEYWORDS:

LQT1; diagnosis; exercise; genetics; genotype; long-QT syndrome; phenotype

PMID:
23691991
DOI:
10.1111/jce.12172
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center