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J Am Heart Assoc. 2012 Apr;1(2):e000570. doi: 10.1161/JAHA.112.000570. Epub 2012 Apr 24.

Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome.

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1
Center for Quantitative Electrocardiography and Cardiac Safety, Heart Research Follow-Up Program, University of Rochester Medical Center, NY (J.-P.C., X.X., A.J.M., W.Z.).

Abstract

BACKGROUND:

Genotype-phenotype investigations have revealed significantly larger risk for cardiac events in patients with type 1 long-QT syndrome (LQT-1), particularly in adult females, with missense mutation in the cytoplasmic loop (C-loop) regions of the α subunit of the KCNQ1 gene associated with an impaired ion channel activation by adrenergic stimulus. We hypothesize that the impaired response to increases in heart rate leads to abnormal QT-RR dynamic profiles and is responsible for the increased cardiac risk for these patients.

METHODS AND RESULTS:

We measured the QT-RR slope in 24-hour Holter ECGs from LQT-1 patients with the mutations associated with impaired adrenergic stimulus (C-loop, n=18) and compared to LQT-1 patients with other mutations (non-C-loop, n=48), and to a healthy control group (n=195). The diurnal QT-RR slope was less steep in C-loop mutation patients (0.10±0.05) than in the ECGs from non-C-loop mutation patients (0.17±0.09, P=0.002). For female patients, slower heart rates were associated with prolonged QT and increased QT-RR slope. Male patients with C-loop mutations showed an impaired repolarization for shorter range of heart rates than in females, which is consistent with gender differences in triggers for events in this syndrome.

CONCLUSIONS:

Our observations suggest that the C-loop LQT-1 patients have specific impaired adrenergic regulation of the ventricular repolarization. This response to heart rate increases may be useful in identification of high-risk patients with inherited prolonged QT and may help select an optimal antiarrhythmic therapeutic strategy. (J Am Heart Assoc. 2012;1:e000570 doi: 10.1161/JAHA.112.000570.).

KEYWORDS:

KCNQ1; QT interval; QT-RR dynamicity; electrocardiogram; long-QT syndrome

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