Apart from clinical symptoms the diagnosis and risk stratification in long-QT syndrome
(LQTS) is usually based on the surface electrocardiogram. Studies have indicated that
not only prolongation of the QT interval but also an increased short-term variability
of QT interval (STVQT) is a marker for a decreased repolarization reserve in patients with drug-induced
LQTS. The aims of this study were to determine if STVQT (1) is higher in patients with LQTS compared with controls, (2) if this effect is
more pronounced in a high-risk LQTS population, and (3) could increase the diagnostic
power of the surface electrocardiogram in identifying mutation carriers. Forty mutation
carriers were compared with age- and gender-matched control subjects in the absence
of β-receptor–blocking agents. Lead II or V5 RR and QT intervals from 30 consecutive beats were manually measured. STVQT was determined from Poincaré plots of QT intervals (STVQT = Σ|QTn + 1 − QTn|/[30 × √2]). Compared with controls, patients with LQTS had a prolonged
QTc interval (449 ± 41 vs 411 ± 32 ms, p = 0.00049) and increased STVQT (6.4 ± 3.2 vs 4.1 ± 1.6 ms, p = 0.005). In patients with the highest risk of clinical
events, defined as a QTc interval >500 ms or symptoms before β-blocker therapy, STVQT was 9 ± 4 ms. QTc interval had a sensitivity of 43% and a specificity of 97% in identifying
mutation carriers (thresholds 450 ms for men and 460 ms for women). Receiver operator
characteristic analysis showed that an STVQT of 4.9 ms was the optimal cut-off value to predict mutation carriers. When incorporating
an STVQT >4.9 ms for those whose QTc interval was within the normal limits, sensitivity to
distinguish mutation carriers increased to 83% with a specificity of 68%, so that
another 15 mutation carriers could be identified. In conclusion, these are the first
results in humans showing that STVQT is increased in congenital LQTS, this effect is increased in patients with symptoms
before therapy, and, hence, STVQT could prove to be a useful noninvasive additive marker for diagnostic screening to
bridge the gap before results of genetic testing are available.
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Article Info
Publication History
Published online: March 20, 2009
Accepted:
January 13,
2009
Received in revised form:
January 13,
2009
Received:
October 19,
2008
Footnotes
Dr. Beckman received support from the German Federal Ministry of Education and Research in the context of German National Genome Research Network Grants 01GS0499 and 01GS0838 to Dr. Kääb who also received a grant from the Fondation Leducq, Paris, France. The KORA platform is funded by the German Federal Ministry of Education and Research and the State of Bavaria. Dr. Thomsen received funding from the Heart Rhythm Society fellowship program and CONTICA (Grant EUFP6-STREP-LSHM-CT-2005-018802).
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© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
