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QT Dynamics During Exercise in Asymptomatic Children with Long QT Syndrome Type 3

Pediatric Cardiology volume 37, pages 860–867 (2016)Cite this article

Abstract

Sympathetic provocative testing is commonly used to detect the abnormal QT dynamics in long QT syndrome (LQTS) patients, particularly LQTS type 1 and type 2. However, little is known about LQTS type 3 (LQT3). We investigated QT dynamics during exercise testing in LQTS patients, particularly LQT3. This study included 37 subjects, comprising 16 genotyped LQTS patients and 21 unrelated healthy subjects without QT prolongation. LQTS patients were divided into LQT3 and non-LQT3 groups. During exercise tests using a modified Bruce protocol, 12-lead electrocardiogram monitoring was performed using a novel multifunctional electrocardiograph. QT intervals were automatically measured. The QT/heart rate (HR) relationship was visualized by plotting the beat-to-beat confluence of the recorded data. A linear regression analysis was performed to determine the QT/HR slope and intercept. Estimated QT intervals at HR 60 bpm (QT60) were calculated by the regression line formula. QT/HR slopes were steeper for each LQTS group than for the control group (P < 0.001). QT60 values demonstrated a moderate correlation with QT intervals at rest (P < 0.0001) for both groups. The corrected QT intervals (QTc) at 4 min of recovery after exercise were significantly longer in the non-LQT3 group than in the control group but were not different between the LQT3 and the control groups. Abnormal QT dynamics during exercise testing were observed in both LQT3 patients and other LQTS subtypes. This method may be useful for directing genetic testing in subjects with borderline prolonged QT intervals.

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References

  1. Ackerman MJ, Khositseth A, Tester DJ et al (2002) Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome. Mayo Clin Proc 77:413–421

    CAS  Article  PubMed  Google Scholar 

  2. Aziz PF, Wieand TS, Ganley J et al (2011) Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome. Circ Arrhythm Electrophysiol 4:867–873

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chauhan VS, Krahn AD, Mitoff P et al (2004) Sudden intense exercise increases QT heart rate slope and T wave complexity in long QT syndrome and normal subjects. Pacing Clin Electrophysiol 27:1415–1423

    Article  PubMed  Google Scholar 

  4. Crotti L, Spazzolini C, Porretta AP et al (2012) Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome. J Am Coll Cardiol 60:2515–2524

    Article  PubMed  PubMed Central  Google Scholar 

  5. Davey P (1999) A new physiological method for heart rate correction of the QT interval. Heart 82:183–186

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Fridericia LS (1920) Die systolendauer im electrocardiogramm bei normaln Menschen und bei Herzkranken. Acta Med Scan 53:469–486

    Article  Google Scholar 

  7. Hekkala AM, Viitasalo M, Väänänen H et al (2010) Abnormal repolarization dynamics revealed in exercise test in long QT syndrome mutation carriers with normal resting QT interval. Europace 12:1296–1301

    Article  PubMed  Google Scholar 

  8. Hekkala AM, Heikki V, Heikki S et al (2012) T-wave morphology after epinephrine bolus may reveal silent long QT syndrome mutation carriers. J Electrocardiol 45:368–372

    Article  PubMed  Google Scholar 

  9. Horner JM, Horner MM, Ackerman MJ (2011) The diagnostic utility of recovery phase QTc during treadmill exercise stress testing in the evaluation of long QT syndrome. Heart Rhythm 8:1698–1704

    Article  PubMed  Google Scholar 

  10. Kligfield P, Lax KG, Okin PM (1996) QT interval-heart rate relation during exercise in normal men and women: definition by linear regression analysis. J Am Coll Cardiol 28:1547–1555

    CAS  Article  PubMed  Google Scholar 

  11. Krahn AD, Klein GJ, Yee R (1997) Hysteresis of the RT interval with exercise: a new marker for the long-QT syndrome? Circulation 96:1551–1556

    CAS  Article  PubMed  Google Scholar 

  12. Magnano AR, Holleran S, Ramakrishnan R et al (2002) Autonomic nervous system influences on QT interval in normal subjects. J Am Coll Cardiol 39:1820–1826

    Article  PubMed  Google Scholar 

  13. Nagatomo T, January CT, Ye B et al (2002) Rate-dependent QT shortening mechanism for the LQT3 deltaKPQ mutant. Cardiovasc Res 54:624–629

    CAS  Article  PubMed  Google Scholar 

  14. Noda T, Takaki H, Kurita T et al (2002) Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome. Eur Heart J 23:975–983

    CAS  Article  PubMed  Google Scholar 

  15. Paavonen KJ, Swan H, Piippo K et al (2001) Response of the QT interval to mental and physical stress in types LQT1 and LQT2 of the long QT syndrome. Heart 86:39–44

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Schwartz PJ, Crotti L (2011) QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation 124:2181–2184

    Article  PubMed  Google Scholar 

  17. Schwartz PJ, Moss AJ, Vincent GM et al (1993) Diagnostic criteria for the long QT syndrome. An update. Circulation 88:782–784

    CAS  Article  PubMed  Google Scholar 

  18. Schwartz PJ, Priori SG, Locati EH et al (1995) Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation 92:3381–3386

    CAS  Article  PubMed  Google Scholar 

  19. Shimizu W, Antzelevitch C (2000) Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol 35:778–786

    CAS  Article  PubMed  Google Scholar 

  20. Shimizu W, Antzelevitch C (2000) Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. Am Coll Cardiol 35:778–786

    CAS  Article  Google Scholar 

  21. Shimizu W, Noda T, Takaki H et al (2003) Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. J Am Coll Cardiol 41:633–642

    CAS  Article  PubMed  Google Scholar 

  22. Shimizu W, Noda T, Takaki H et al (2004) Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome. Heart Rhythm 1:276–283

    Article  PubMed  Google Scholar 

  23. Slinker BK, Glantz SA (1988) Multiple linear regression is a useful alternative to traditional analyses of variance. Am J Physiol 255:R353–R367

    CAS  PubMed  Google Scholar 

  24. Sundaram S, Carnethon M, Polito K et al (2008) Autonomic effects on QT-RR interval dynamics after exercise. Am J Physiol Heart Circ Physiol 294:H490–H497

    CAS  Article  PubMed  Google Scholar 

  25. Swan H, Toivonen L, Viitasalo M (1998) Rate adaptation of QT intervals during and after exercise in children with congenital long QT syndrome. Eur Heart J 19:508–513

    CAS  Article  PubMed  Google Scholar 

  26. Swan H, Viitasalo M, Piippo K et al (1999) Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects. J Am Coll Cardiol 34:823–829

    CAS  Article  PubMed  Google Scholar 

  27. Sy RW, van der Werf C, Chattha IS et al (2011) Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands. Circulation 124:2187–2194

    Article  PubMed  Google Scholar 

  28. Takahashi K, Shimizu W, Miyake A et al (2014) High prevalence of the SCN5A E1784 K mutation in school children with long QT syndrome living on the Okinawa islands. Circ J 78:1974–1979

    CAS  Article  PubMed  Google Scholar 

  29. Takahashi K, Nabeshima T, Sashinami A et al (2015) QT dynamics evaluated by fully automated QT measurements in children. Ped Int. doi:10.1111/ped.12734

    Google Scholar 

  30. Takenaka K, Ai T, Shimizu W et al (2003) Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome. Circulation 107:838–844

    Article  PubMed  Google Scholar 

  31. Variability Merri M QT (1996) In: Moss AJ, Stern S (eds) Noninvasive electrocardiology: clinical aspects of Holter monitoring. WB Saunders, London

    Google Scholar 

  32. Vyas H, Ackerman MJ (2006) Epinephrine QT stress testing in congenital long QT syndrome. J Electrocardiol 39:S107–S113

    Article  PubMed  Google Scholar 

  33. Vyas H, Hejlik J, Ackerman MJ et al (2006) Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response. Circulation 113:1385–1392

    CAS  Article  PubMed  Google Scholar 

  34. Walker BD, Krahn AD, Klein GJ et al (2005) Burst bicycle exercise facilitates diagnosis of latent long QT syndrome. Am Heart J 150:1059–1063

    Article  PubMed  Google Scholar 

  35. White DW, Raven PB (2014) Autonomic neural control of heart rate during dynamic exercise: revisited. J Physiol 592:2491–2500

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Wong JA, Gula LJ, Klein GJ et al (2010) Utility of treadmill testing in identification and genotype prediction in long-QT syndrome. Circ Arrhythm Electrophysiol 3:120–125

    Article  PubMed  Google Scholar 

  37. Zareba W (2010) Challenges of diagnosing long QT syndrome in patients with nondiagnostic resting QTc. J Am Coll Cardiol 55:1962–1964

    Article  PubMed  Google Scholar 

  38. Zareba W, Moss AJ, Locati EH et al (2003) Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol 42:103–109

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Prof. Shimizu for providing the genetic data and the technicians in the physiology laboratory for their cooperation in data acquisition. The authors would like to thank Enago (www.enago.jp) for the English language review.

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  1. Department of Pediatric Cardiology, Okinawa Children’s Medical Center, 118-1 Arakawa, Haebaru-chou, Okinawa, 901-1193, Japan

    Kazuhiro Takahashi, Taisuke Nabeshima, Mami Nakayashiro & Hitoshi Ganaha

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  1. Kazuhiro Takahashi
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  2. Taisuke Nabeshima
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  3. Mami Nakayashiro
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  4. Hitoshi Ganaha
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Correspondence to Kazuhiro Takahashi.

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Takahashi, K., Nabeshima, T., Nakayashiro, M. et al. QT Dynamics During Exercise in Asymptomatic Children with Long QT Syndrome Type 3. Pediatr Cardiol 37, 860–867 (2016). https://doi.org/10.1007/s00246-016-1360-4

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  • DOI: https://doi.org/10.1007/s00246-016-1360-4

Keywords

  • Ventricular repolarization
  • Long QT syndrome
  • Exercise test
  • QT dynamics