Yonsei Med J.  2013 Mar;54(2):529-533. 10.3349/ymj.2013.54.2.529.

A Case of Long QT Syndrome Type 3 Aggravated by Beta-Blockers and Alleviated by Mexiletine: The Role of Epinephrine Provocation Test

• Park J
• Kim SK
• Pak HN

• KMID: 1503921
• DOI: http://doi.org/10.3349/ymj.2013.54.2.529

Abstract

Long QT syndrome (LQTs) is an uncommon genetic disease causing sudden cardiac death with Torsade de Pointes (TdP). The first line drug treatment has been known to be beta-blocker. We encountered a 15-year-old female student with LQTs who had prolonged QTc and multiple episodes of syncope or agonal respiration during sleep. Although her T wave morphology in surface electrocardiography resembled LQTs type 1, her clinical presentation was unusual. During the epinephrine test, TdP was aggravated during beta-blocker medication, but alleviated by sodium channel blocker (mexiletine). Therefore, she underwent implantable cardioverter defibrillator implantation.

Keyword

Long QT syndrome type 3; torsade de pointes; beta-blocker; mexiletine; SCN5A

MeSH Terms

Adolescent
Adrenergic beta-Antagonists/*adverse effects/therapeutic use
Defibrillators, Implantable
Diagnosis, Differential
Diagnostic Techniques, Cardiovascular
Epinephrine/*diagnostic use
Female
Humans
Long QT Syndrome/classification/*diagnosis/genetics/therapy
Mexiletine/*therapeutic use
Pedigree
*Syncope
Adrenergic beta-Antagonists
Mexiletine
Epinephrine

Figure

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  Fig. 1 (A) Baseline standard 12 lead ECG shows prolonged QTc interval (629 ms). (B) 12 ECG shows premature ventricular contraction which was originated from left ventriclular basal posteroseptum, related to earlier VSD repair. ECG, electrocardiography; VSD, ventricular septal defect.

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  Fig. 2 The genetic pedigree of the patient shows that her grandmother died from pancreatic cancer, and there was no family history of sudden death.

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  Fig. 3 The ECG documented events during epinephrine provocation test. (A) Baseline epinephrine provocation test showing non-sustained VT with maximal 3 beats of extra-systole. (B) While taking propranolol 120 mg, non-sustained polymorphic VT was repeatedly documented during epinephrine infusion. (C) While taking propranolol 160 mg, torsade de pointes requiring cardioversion was spontaneously induced during epinephrine infusion. (D) After stopping propranolol, only isolated ventricular premature beats were induced by epinephrine infusion. (E) During medication with mexiletine 600 mg per day, the epinephrine provocation test showed no event except for QTc lengthening >30 ms. ECG, electrocardiography; VT, ventricular tachycardia.

Reference

1. Lim SM, Pak HN, Lee MH, Kim SS, Joung B. Fever-induced QTc prolongation and ventricular fibrillation in a healthy young man. Yonsei Med J. 2011. 52:1025–1027.

2. Shimizu W, Noda T, Takaki H, Kurita T, Nagaya N, Satomi K, et al. Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. J Am Coll Cardiol. 2003. 41:633–642.

3. Shimizu W, Noda T, Takaki H, Nagaya N, Satomi K, Kurita T, et al. Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome. Heart Rhythm. 2004. 1:276–283.

4. Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, et al. Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009. 120:1752–1760.

5. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001. 103:89–95.

6. Priori SG, Napolitano C, Paganini V, Cantù F, Schwartz PJ. Molecular biology of the long QT syndrome: impact on management. Pacing Clin Electrophysiol. 1997. 20(8 Pt 2):2052–2057.

7. Priori SG, Napolitano C, Schwartz PJ, Grillo M, Bloise R, Ronchetti E, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA. 2004. 292:1341–1344.

8. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000. 102:1178–1185.

9. Bennett PB, Yazawa K, Makita N, George AL Jr. Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995. 376:683–685.

10. Wang DW, Yazawa K, Makita N, George AL Jr, Bennett PB. Pharmacological targeting of long QT mutant sodium channels. J Clin Invest. 1997. 99:1714–1720.

11. Fabritz L, Kirchhof P, Franz MR, Nuyens D, Rossenbacker T, Ottenhof A, et al. Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in DeltaKPQ SCN5A (long QT3) mice. Cardiovasc Res. 2003. 57:1085–1093.

12. Benhorin J, Taub R, Goldmit M, Kerem B, Kass RS, Windman I, et al. Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long-QT syndrome? Circulation. 2000. 101:1698–1706.

13. Gellens ME, George AL Jr, Chen LQ, Chahine M, Horn R, Barchi RL, et al. Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci U S A. 1992. 89:554–558.

14. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998. 392:293–296.

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

16. Wang Q, Chen S, Chen Q, Wan X, Shen J, Hoeltge GA, et al. The common SCN5A mutation R1193Q causes LQTS-type electrophysiological alterations of the cardiac sodium channel. J Med Genet. 2004. 41:e66.

17. Vatta M, Dumaine R, Varghese G, Richard TA, Shimizu W, Aihara N, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet. 2002. 11:337–345.

18. Ackerman MJ, Splawski I, Makielski JC, Tester DJ, Will ML, Timothy KW, et al. Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing. Heart Rhythm. 2004. 1:600–607.

19. Makita N, Behr E, Shimizu W, Horie M, Sunami A, Crotti L, et al. The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome. J Clin Invest. 2008. 118:2219–2229.