T wave morphology analysis distinguishes between KvLQT1 and HERG mutations in long QT syndrome.
OBJECTIVE
The aim of this study was to develop an objective method to distinguish between HERG and KvLQT1 genotypes on the surface ECG.


BACKGROUND
The two most prevalent genes affected in long QT syndrome (LQTS) are KvLQT1 (KCNQ1) and HERG (KCNH2), which are mutated in >90% of patients with a reported LQTS genotype. It is known that T waves have lower amplitude and more notches in HERG patients than T waves in KvLQT1 patients, but this semiquantitative method lacks the discriminative power to be used in a clinical setting. We developed a simple mathematical method that allowed us to quantify T wave shape in LQTS mutations for clinical use.


METHODS
ECGs from 24 HERG patients, 13 KvLQT1 LQTS patients, and 13 healthy relatives were examined. The repolarizing integral (RI) was constructed from the T wave. The resulting RI is sigmoid and was modeled using the Hill equation as (RI(t) = V(max)*[t(n)/[K(m)(n) + t(n)]]). V(max) is equivalent to the total T wave area, K(m) is the time when 50% of the T wave area is reached, and n is a measure of the slope of the sigmoid RI.


RESULTS
The RI correlated nearly perfectly to the fitted sigmoid, r = 0.99. In lead V(2), V(max) was larger in KvLQT1 (0.148 +/- 0.021) (mean +/- SE) compared to HERG (0.080 +/- 0.012) and controls (0.067 +/- 0.021). The Hill coefficient n of the RI discriminated perfectly between HERG (2.00 +/- 0.11) and KvLQT1 (4.11 +/- 0.15).


CONCLUSIONS
RI allows distinguishing between HERG and KvLQT1 mutations based solely on the T wave morphology in the present LQTS population.
Kanters
Jørgen K
JK
Department of Medicine, Elsinore Hospital, Helsingør, Denmark. jkanters@mfi.ku.dk
Fanoe
Søren
S
Larsen
Lars A
LA
Bloch Thomsen
Poul Erik
PE
Toft
Egon
E
Christiansen
Michael
M
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D003937:Diagnosis, Differential; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D005838:Genotype; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated