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01-06-2016 | Original Article

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

Authors: Kazuhiro Takahashi, Taisuke Nabeshima, Mami Nakayashiro, Hitoshi Ganaha

Published in: Pediatric Cardiology | Issue 5/2016

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.

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 77:413–421CrossRefPubMed

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 4:867–873CrossRefPubMedPubMedCentral

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 27:1415–1423CrossRefPubMed

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 60:2515–2524CrossRefPubMedPubMedCentral

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

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

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 12:1296–1301CrossRefPubMed

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 45:368–372CrossRefPubMed

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 8:1698–1704CrossRefPubMed

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 28:1547–1555CrossRefPubMed

11.

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

12.

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

13.

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

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 23:975–983CrossRefPubMed

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 86:39–44CrossRefPubMedPubMedCentral

16.

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

17.

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

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 92:3381–3386CrossRefPubMed

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 35:778–786CrossRefPubMed

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 35:778–786CrossRef

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 41:633–642CrossRefPubMed

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 1:276–283CrossRefPubMed

23.

Slinker BK, Glantz SA (1988) Multiple linear regression is a useful alternative to traditional analyses of variance. Am J Physiol 255:R353–R367PubMed

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–H497CrossRefPubMed

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 19:508–513CrossRefPubMed

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 34:823–829CrossRefPubMed

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 124:2187–2194CrossRefPubMed

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 78:1974–1979CrossRefPubMed

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

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 107:838–844CrossRefPubMed

31.

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

32.

Vyas H, Ackerman MJ (2006) Epinephrine QT stress testing in congenital long QT syndrome. J Electrocardiol 39:S107–S113CrossRefPubMed

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 113:1385–1392CrossRefPubMed

34.

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

35.

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

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 3:120–125CrossRefPubMed

37.

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

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 42:103–109CrossRefPubMed

Title: QT Dynamics During Exercise in Asymptomatic Children with Long QT Syndrome Type 3
Authors: Kazuhiro Takahashi
Taisuke Nabeshima
Mami Nakayashiro
Hitoshi Ganaha
Publication date: 01-06-2016
Publisher: Springer US
Published in: Pediatric Cardiology / Issue 5/2016
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI: https://doi.org/10.1007/s00246-016-1360-4

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