HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies

Ackerman, Michael J.; Priori, Silvia G.; Willems, Stephan; Berul, Charles I.; Brugada, Ramón; Calkins, Hugh; Camm, A. John; Ellinor, Patrick T.; Gollob, Michael H.; Hamilton, Robert M.; Hershberger, Ray E.; Judge, Daniel P.; Marec, Hervé Le; McKenna, William J.; Schulze‐Bahr, Eric; Semsarian, C.; Towbin, Jeffrey A.; Watkins, Hugh; Wilde, Arthur A.M.; Wolpert, Christian; Zipes, Douglas P.

doi:10.1016/j.hrthm.2011.05.020

Cited by 1,083 publications

(705 citation statements)

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“…Many at‐risk individuals are likely to be unaware of their status in light of the disorder's incomplete penetrance, variable expressivity, and unpredictable course 6, 26. The risk of life‐threatening cardiac events is highest in young adolescence, and identification of a pathogenic variant in an LQTS gene has the potential to prevent life‐threatening cardiac events in offspring or siblings 7, 27…”

Section: Discussionmentioning

confidence: 99%

“…It was noted whether the patients with a pathogenic or likely pathogenic variant and the patients with variants of uncertain significance (VUS) met the criteria for a clinical diagnosis of LQTS on the basis of current guidelines 2, 7. The LQTS risk score (Schwartz) was based on QTc from ECG 2 because it was least affected by environmental factors 2, 10.…”

Section: Methodsmentioning

confidence: 99%

“…Autosomal dominant is the most common inheritance pattern, and KCNQ1 (LQT1) harbors most genetic defects, followed by KCNH2 (LQT2) and SCN5A (LQT3) 6, 7. Penetrance is incomplete, and expression is variable within families; these factors complicate both interpretation of pathogenicity of sequence variants in LQTS genes and genetic counseling 8…”

Section: Introductionmentioning

confidence: 99%

“…Current guidelines recommend genetic testing of asymptomatic patients if repetitive ECGs show a QTc ≥480 ms (European Society of Cardiology guidelines2) or a QTc >500 ms (Heart Rhythm Society/European Heart Rhythm Association Expert Consensus Statement7) in the absence of secondary causes that may prolong the QT interval. An LQTS risk score (Schwartz) >3 is also considered diagnostic 2, 7, 10.…”

Section: Introductionmentioning

confidence: 99%

“…An LQTS risk score (Schwartz) >3 is also considered diagnostic 2, 7, 10. In accordance with current clinical guidelines for LQTS, genetic analyses have often been limited to the 3 main LQTS genes.…”

Section: Introductionmentioning

confidence: 99%

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Genetic and Phenotypic Characterization of Community Hospital Patients With QT Prolongation

Gibbs

Thalamus

Tveten

et al. 2018

JAHA

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BackgroundCongenital long‐QT syndrome (LQTS) is a genetic disorder characterized by prolongation of the corrected QT interval (QTc) on an ECG. The aim of the present study was to estimate the prevalence of pathogenic and likely pathogenic sequence variants in patients who had at least 1 ECG with a QTc ≥500 ms.Methods and ResultsTelemark Hospital Trust is a community hospital within the Norwegian national health system, serving ≈173 000 inhabitants. We searched the ECG database at Telemark Hospital Trust, Norway, from January 2004 to December 2014, and identified 1531 patients with at least 1 ECG with a QTc ≥500 ms. At the time of inclusion in this study (2015), 766 patients were alive. A total of 733 patients were invited to participate, and 475 accepted. The 17 genes that have been reported to cause monogenic LQTS were sequenced among the patients. Pro‐QTc score was calculated for each patient. A molecular genetic cause of LQTS was detected in 31 (6.5%) of 475 patients. These patients had a lower pro‐QTc score than those without pathogenic or likely pathogenic variants (1.7±1.0 versus 2.8±1.6; P<0.001).ConclusionsCompared with the general population, hospitalized patients with a QTc ≥500 ms in at least 1 ECG recording had an increased likelihood for pathogenic and likely pathogenic variants in LQTS genes. We recommend increased awareness of the possibility of LQTS in patients with at least 1 ECG with a QTc ≥500 ms.

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