Long QT Syndrome Exposed by Effort

AAM Wilde, TA Simmers. Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam (The Netherlands)

Case Reports

A 14-year old boy suddenly died while playing soccer. He was in the middle of a sprint when he suddenly succumbed. Resuscitation efforts were unsuccessful. His family assured that he had been without complaints before and that his family history was unremarkable. A two year older brother, however, remembered that he had also collapsed once while playing an exciting soccer match. This occurred at the age of 10, after which he experienced no further events. His brother’s death worried him (and his family) and he visited a cardiologist for medical advice

Physical examination was unremarkable; his ECG is shown in Fig 1. The ECG shows sinus rhythm (70 bpm) with a normal QRS axis. PQ interval and QRS width are normal. Repolarization is completely normal and the QTc-interval is 384 msec, well within normal limits. Hence the ECG is completely normal. An echocardiogram was also normal.

From the history of the patient and from his family history it became clear that both events (his collapse and the circumstances of his brother’s death) were triggered by exercise. An exercise test should therefore be part of the cardiological work-up.

Figure 2 shows the ECG after 6 minutes of exercise. There is still sinus rhythm, 130 bpm, and conduction intervals remain normal. The QT-interval is now markedly prolonged and approaches 530 msec (QTc: 527 msec). This response should raise suspicion on a long QT syndrome, type 1 and in conjunction with the complaint(s) of the patient ß-blockade therapy is warranted. Molecular genetic screening indeed revealed a mutation in the KCNQ1 gene.

long-QT normal baseline ECG
Figure 1. Baseline ECG (see text)
long-QT syndrome effort ECG
Figure 2. ECG during effort test (see text)

Editor's Comments

The congenital long QT syndrome (LQTS) is a genetically transmitted disease. Mutations causing LQTS have been identified in 5 genes each encoding a cardiac ion channel and its regulatory subunit [1] . LQT1 is caused by mutations in the KCNQ1 gene encoding a potassium channel conducting the IKs potassium current.

Detection of QTc prolongation in the basal ECG is the hallmark feature in the diagnosis of LQTS. However, studies that investigated QTc in genotyped LQTS families reported LQT1 patients having disease-causing mutations despite a normal QTc [2][3][4].

Type 1 LQTS is characterized by QT-prolongation, in particular during exercise. The QT-interval fails to adapt to an increase in rate and therefore inappropriately prolongs during exercise [5][6]. In conjunction, events (dizziness, syncope and sudden death) are typically triggered by adrenergic stimuli like exercise, diving and swimming [7], the age of onset of complaints is usually around 5 years. The present case exemplifies a LQT1 patient in whom QT prolongation only may be detected during an exercise test. In these cases, a careful family history should be taken and molecular genetic screening is mandatory. In symptomatic patients with LQT1, treatment of choice is a ß-blocker titrated up to the highest possible tolerated dose [8][9]. Asymptomatic young patients should receive prophylactic treatment but asymptomatic individuals over 20 years of age with a QTc interval < 500 msec seem to be at low risk (see also case III-6).

References

  1. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, and Keating MT. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. PubMed ID:10973849 
  2. Vincent GM, Timothy KW, Leppert M, and Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N Engl J Med. 1992 Sep 17;327(12):846-52. DOI:10.1056/NEJM199209173271204 | PubMed ID:1508244
  3. Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Robinson JL, Priori SG, Benhorin J, Locati EH, Towbin JA, Keating MT, Lehmann MH, and Hall WJ. Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med. 1998 Oct 1;339(14):960-5.DOI:10.1056/NEJM199810013391404 | PubMed ID:9753711
  4. Priori SG, Napolitano C, and Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation. 1999 Feb 2;99(4):529-33. PubMed ID:9927399
  5. Vincent GM, Jaiswal D, and Timothy KW. Effects of exercise on heart rate, QT, QTc and QT/QS2 in the Romano-Ward inherited long QT syndrome. Am J Cardiol. 1991 Aug 15;68(5):498-503. PubMed ID:1872278
  6. Moretti P; Calcaterra G, Napolitano C, et al. High prevalence of concealed long QT syndrome among carriers of KVLQT1 defects. Circulation 2001; 201 (Suppl): II-584 (abstract).
  7. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AA, Toivonen L, Zareba W, Robinson JL, Timothy KW, Corfield V, Wattanasirichaigoon D, Corbett C, Haverkamp W, Schulze-Bahr E, Lehmann MH, Schwartz K, Coumel P, and Bloise R. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001 Jan 2;103(1):89-95. PubMed ID:11136691
  8. Villain E, Denjoy I, Lupoglazoff JM, Guicheney P, Hainque B, Lucet V, and Bonnet D. Low incidence of cardiac events with beta-blocking therapy in children with long QT syndrome. Eur Heart J. 2004 Aug;25(16):1405-11. DOI:10.1016/j.ehj.2004.06.016 | PubMed ID:15321698
  9. Priori SG, Aliot E, Blomstrom-Lundqvist C, Bossaert L, Breithardt G, Brugada P, Camm AJ, Cappato R, Cobbe SM, Di Mario C, Maron BJ, McKenna WJ, Pedersen AK, Ravens U, Schwartz PJ, Trusz-Gluza M, Vardas P, Wellens HJ, and Zipes DP. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J. 2001 Aug;22(16):1374-450. DOI:10.1053/euhj.2001.2824 | PubMed ID:11482917
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