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End‐Recovery QTc: A Useful Metric for Assessing Genetic Variants of Unknown Significance in Long‐QT syndrome
Author(s) -
OBEYESEKERE MANOJ N.,
SY RAYMOND W.,
KLEIN GEORGE J.,
GULA LORNE J.,
MODI SIMON,
CONACHER SUSAN,
LEONGSIT PETER,
SKANES ALLAN C.,
YEE RAYMOND,
KRAHN ANDREW D.
Publication year - 2012
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2011.02265.x
Subject(s) - medicine , long qt syndrome , qt interval , clinical significance , cardiology , single nucleotide polymorphism , genetic testing , genotype , genetics , gene , biology
QTc for Assessing Significance of LQT Variants. Introduction: Genetic variants represent benign single‐nucleotide polymorphisms, disease causing mutations or variants of unknown significance (VUS). Resting, exercise, and recovery QTc intervals have been utilized to detect long‐QT syndrome (LQTS) mutations. We sought to provide clinical data that may assist in classifying the presented VUS as disease causing/benign and to determine whether resting and/or end‐recovery QT parameters can evaluate the significance of VUS. Methods and Results: Twenty‐six patients with a VUS in genes associated with LQTS (15 females, age 38 ± 16 years) and 26 age and gender matched controls (age 37 ± 20 years) were included. There were 10 VUS (5 KCNQ1, 4 KCNH2, 1 KCNE1) in 12 families. All but 1 VUS was associated with sudden cardiac death (SCD), aborted SCD or Torsade de pointes. A Schwartz score of ≥3.5 was observed in at least 1 family member with each VUS. Resting QTc was marginally longer in VUS patients compared with controls (458 ± 48 vs 437 ± 25, P = 0.052). A prolonged resting QTc (>470 ms males, >480 ms females) identified 6 VUS carriers and 1 control. VUS carriers had a substantially longer end‐recovery QTc (502 ± 68 vs 427 ± 17, P < 0.01) with an end‐recovery QTc > 445 ms in 20/26 VUS patients compared to 2/26 controls (P < 0.01). The area under the receiver operating characteristic curve for resting QTc was 0.68 (95% CI, 0.53–0.83, P = 0.03) compared to the end‐recovery QTc of 0.88 (95% CI, 0.76–0.99, P < 0.0001). Conclusion: Variants in the current study appear to be disease causing. The end‐recovery QTc is a useful metric when interpreting LQT VUS. (J Cardiovasc Electrophysiol, Vol. 23, pp. 637–642, June 2012)