Advertisement

Relation of Increased Short-Term Variability of QT Interval to Congenital Long-QT Syndrome

      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Moss A.J.
        • Kass R.S.
        Long QT syndrome: from channels to cardiac arrhythmias.
        J Clin Invest. 2005; 115: 2018-2024
        • Schwartz P.J.
        The congenital long QT syndromes from genotype to phenotype: clinical implications.
        J Intern Med. 2006; 259: 39-47
        • Keating M.T.
        • Sanguinetti M.C.
        Molecular and cellular mechanisms of cardiac arrhythmias.
        Cell. 2001; 104: 569-580
        • Sanguinetti M.C.
        • Tristani-Firouzi M.
        HERG potassium channels and cardiac arrhythmia.
        Nature. 2006; 440: 463-469
        • Marbán E.
        Cardiac channelopathies.
        Nature. 2002; 415: 213-218
        • Roden D.M.
        Long QT syndrome: reduced repolarization reserve and the genetic link.
        J Intern Med. 2006; 259: 59-69
        • Roden D.M.
        Taking the idio out of idiosyncratic-predicting torsades de pointes.
        Pacing Clin Electrophysiol. 1998; 21: 1029-1034
        • Roden D.M.
        Clinical practice.
        N Engl J Med. 2008; 358: 169-176
        • Vincent G.M.
        • Timothy K.W.
        • Leppert M.
        • Keating M.
        The spectrum of symptoms and QT intervals in carriers of gene for the long QT-syndrome.
        N Engl J Med. 1992; 327: 846-852
        • Priori S.G.
        • Schwartz P.J.
        • Napolitano C.
        • Bloise R.
        • Ronchetti E.
        • Grillo M.
        • Vicentini A.
        • Spazzolini C.
        • Nastolli J.
        • Bottelli G.
        • Folli R.
        • Cappelletti D.
        Risk stratification in the long-QT syndrome.
        N Engl J Med. 2003; 348: 1866-1874
        • Priori S.G.
        • Napolitano C.
        • Schwartz P.J.
        Low penetrance in the long-QT syndrome: clinical impact.
        Circulation. 1999; 99: 529-533
        • Shimizu W.
        • Noda T.
        • Takaki H.
        • Kurita T.
        • Nagaya N.
        • Satomi K.
        • Suyama K.
        • Aihara N.
        • Kamakura S.
        • Sunagawa K.
        • et al.
        Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome.
        J Am Coll Cardiol. 2003; 41: 633-642
        • Hinterseer M.
        • Thomsen M.B.
        • Beckmann B.M.
        • Pfeufer A.
        • Schimpf R.
        • Wichmann H.E.
        • Steinbeck G.
        • Vos M.A.
        • Kaab S.
        Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome: a case control pilot study.
        Eur Heart J. 2008; 29: 185-190
        • Holle R.
        • Happich M.
        • Löwel H.
        • Wichmann H.E.
        • MONICA/KORA Study Group
        KORA—a research platform for population based health research.
        Gesundheitswesen. 2005; 67: 19-25
        • Lepeschkin E.
        • Surawicz B.
        The measurement of the Q-T interval of the electrocardiogram.
        Circulation. 1952; 6: 378-388
        • Bazett H.C.
        An analysis of the time-relations of electrocardiograms.
        Heart. 1920; 7: 353-370
        • Merri M.
        • Benhorin J.
        • Alberti M.
        • Locati E.
        • Moss A.J.
        Electrocardiographic quantitation of ventricular repolarization.
        Circulation. 1989; 80: 1301-1308
        • Thomsen M.B.
        • Verduyn S.C.
        • Stengl M.
        • Beekman J.D.
        • de Pater G.
        • van Opstal J.
        • Volders P.G.
        • Vos M.A.
        Increased short-term variability of repolarization predicts d-sotalol–induced torsades de pointes in dogs.
        Circulation. 2004; 110: 2453-2459
        • Splawski I.
        • Shen J.
        • Timothy K.W.
        • Lehmann M.H.
        • Priori S.
        • Robinson J.L.
        • Moss A.J.
        • Schwartz P.J.
        • Towbin J.A.
        • Vincent G.M.
        • Keating M.T.
        Spectrum of mutations in long-QT syndrome genes.
        Circulation. 2000; 102: 1178-1185
        • Mönnig G.
        • Eckardt L.
        • Wedekind H.
        • Haverkamp W.
        • Gerss J.
        • Milberg P.
        • Wasmer K.
        • Kirchhof P.
        • Assmann G.
        • Breithardt G.
        • Schulze-Bahr E.
        Electrocardiographic risk stratification in families with congenital long QT syndrome.
        Eur Heart J. 2006; 27: 2074-2080
        • Hofman N.
        • Wilde A.A.
        • Kääb S.
        • van Langen I.M.
        • Tanck M.W.
        • Mannens M.M.
        • Hinterseer M.
        • Beckmann B.M.
        • Tan H.L.
        Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system?.
        Eur Heart J. 2007; 28: 575-580
        • Pfeufer A.
        • Jalilzadeh S.
        • Perz S.
        • Mueller J.C.
        • Hinterseer M.
        • Illig T.
        • Akyol M.
        • Huth C.
        • Schöpfer-Wendels A.
        • Kuch B.
        • et al.
        Common variants in myocardial ion channel genes modify the QT interval in the general population: results from the KORA study.
        Circ Res. 2005; 96: 693-701
        • Locati E.H.
        • Zareba W.
        • Moss A.J.
        • Schwartz P.J.
        • Vincent G.M.
        • Lehmann M.H.
        • Towbin J.A.
        • Priori S.G.
        • Napolitano C.
        • Robinson J.L.
        • et al.
        Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry.
        Circulation. 1998; 97: 2237-2244