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Short QT syndrome

Charles Antzelevitch, PhD, FACC, FAHA, FHRS
Jonathan M Cordeiro, PhD
Section Editor
Mark S Link, MD
Deputy Editor
Brian C Downey, MD, FACC


Short QT Syndrome (SQTS) is a rare inherited channelopathy (a disorder that affects the movement of ions through channels within the cell membrane) associated with marked shortened QT intervals and sudden cardiac death (SCD) in individuals with a structurally normal heart. In contrast to long QT syndrome, another channelopathy, ion channel defects associated with SQTS lead to abnormal abbreviation of repolarization, predisposing affected individuals to a risk of atrial and ventricular arrhythmias. (See "Pathophysiology of the long QT syndrome".)

Since its first report in 2000, significant progress has been made in defining the genetic and cellular basis of SQTS as well as in therapeutic approaches to treating this syndrome. SQTS is a genetically heterogeneous disease with six different genes encoding various cardiac ion channels thus far identified. Data regarding genotype-phenotype correlation and genotype-specific treatment are promising but limited, primarily due to the lack of clinical cases.

The clinical presentation, diagnostic approach, and treatment modalities for SQTS will be discussed here. SCD and other channelopathies are discussed separately. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Congenital long QT syndrome: Epidemiology and clinical manifestations".)


In 1993, it was first proposed that shorter than normal QT intervals (<400 msec) are associated with a 2.4-fold increased risk for SCD [1]. An abnormally short QT interval observed before and after runs of VT/VF has been reported anecdotally [2,3]. Interestingly, certain species of kangaroo, known to have a high incidence of SCD, display an abnormally short QT interval as a normal feature on their electrocardiogram (ECG) [4,5].

SQTS was first described as a clinical entity in a report of four patients with extremely short QT intervals in association with paroxysmal atrial fibrillation and SCD [6]. In 2003, another study further described SQTS in two unrelated European families (six patients total) with a strong family history of sudden death in association with short QT interval on ECG [7]. Since then, over 100 cases of SQTS have been reported, and the existence of this novel channelopathy has been validated.

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Literature review current through: Nov 2017. | This topic last updated: Nov 08, 2017.
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  1. Algra A, Tijssen JG, Roelandt JR, et al. QT interval variables from 24 hour electrocardiography and the two year risk of sudden death. Br Heart J 1993; 70:43.
  2. Fei L, Camm AJ. Shortening of the QT interval immediately preceding the onset of idiopathic spontaneous ventricular tachycardia. Am Heart J 1995; 130:915.
  3. Kontny F, Dale J. Self-terminating idiopathic ventricular fibrillation presenting as syncope: a 40-year follow-up report. J Intern Med 1990; 227:211.
  4. Campbell TJ. Characteristics of cardiac action potentials in marsupials. J Comp Physiol B 1989; 158:759.
  5. Rezakhani A, Webster JD, Atwell RB. The electrocardiogram of the eastern grey kangaroo (Macropus giganteus). Aust Vet J 1986; 63:310.
  6. Gussak I, Brugada P, Brugada J, et al. Idiopathic short QT interval: a new clinical syndrome? Cardiology 2000; 94:99.
  7. Gaita F, Giustetto C, Bianchi F, et al. Short QT Syndrome: a familial cause of sudden death. Circulation 2003; 108:965.
  8. Cross B, Homoud M, Link M, et al. The short QT syndrome. J Interv Card Electrophysiol 2011; 31:25.
  9. Gollob MH, Redpath CJ, Roberts JD. The short QT syndrome: proposed diagnostic criteria. J Am Coll Cardiol 2011; 57:802.
  10. Rautaharju PM, Zhou SH, Wong S, et al. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol 1992; 8:690.
  11. Gussak I, Antzelevitch C, Goodman D, Bjerregaard P. Short QT interval: ECG phenomenon and clinical syndrome. In: Cardiac Repolarization. Bridging Basic and Clinical Sciences, Gussak I, Antzelevitch C (Eds), Humana Press, Totowa, NJ 2003. p.497.
  12. Gussak I, Bjerregaard P. Short QT syndrome--5 years of progress. J Electrocardiol 2005; 38:375.
  13. Bjerregaard P, Gussak I. Short QT syndrome. Ann Noninvasive Electrocardiol 2005; 10:436.
  14. Bjerregaard P, Gussak I. Short QT syndrome: mechanisms, diagnosis and treatment. Nat Clin Pract Cardiovasc Med 2005; 2:84.
  15. Anttonen O, Junttila MJ, Rissanen H, et al. Prevalence and prognostic significance of short QT interval in a middle-aged Finnish population. Circulation 2007; 116:714.
  16. Kobza R, Roos M, Niggli B, et al. Prevalence of long and short QT in a young population of 41,767 predominantly male Swiss conscripts. Heart Rhythm 2009; 6:652.
  17. Miyamoto A, Hayashi H, Yoshino T, et al. Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population. Heart Rhythm 2012; 9:66.
  18. Mason JW, Ramseth DJ, Chanter DO, et al. Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 2007; 40:228.
  19. Giustetto C, Di Monte F, Wolpert C, et al. Short QT syndrome: clinical findings and diagnostic-therapeutic implications. Eur Heart J 2006; 27:2440.
  20. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004; 109:30.
  21. Cordeiro JM, Brugada R, Wu YS, et al. Modulation of I(Kr) inactivation by mutation N588K in KCNH2: a link to arrhythmogenesis in short QT syndrome. Cardiovasc Res 2005; 67:498.
  22. McPate MJ, Duncan RS, Milnes JT, et al. The N588K-HERG K+ channel mutation in the 'short QT syndrome': mechanism of gain-in-function determined at 37 degrees C. Biochem Biophys Res Commun 2005; 334:441.
  23. Sun Y, Quan XQ, Fromme S, et al. A novel mutation in the KCNH2 gene associated with short QT syndrome. J Mol Cell Cardiol 2011; 50:433.
  24. Templin C, Ghadri JR, Rougier JS, et al. Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J 2011; 32:1077.
  25. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442.
  26. Burashnikov E, Pfeiffer R, Barajas-Martinez H, et al. Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm 2010; 7:1872.
  27. Roussel J, Labarthe F, Thireau J, et al. Carnitine deficiency induces a short QT syndrome. Heart Rhythm 2016; 13:165.
  28. Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci 2004; 1033:42.
  29. Tein I. Role of carnitine and fatty acid oxidation and its defects in infantile epilepsy. J Child Neurol 2002; 17 Suppl 3:3S57.
  30. Ferro F, Ouillé A, Tran TA, et al. Long-chain acylcarnitines regulate the hERG channel. PLoS One 2012; 7:e41686.
  31. Patel C, Antzelevitch C. Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome. Heart Rhythm 2008; 5:585.
  32. Extramiana F, Antzelevitch C. Amplified transmural dispersion of repolarization as the basis for arrhythmogenesis in a canine ventricular-wedge model of short-QT syndrome. Circulation 2004; 110:3661.
  33. Burashnikov A, Antzelevitch C. Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation. Pacing Clin Electrophysiol 2006; 29:290.
  34. McPate MJ, Zhang H, Adeniran I, et al. Comparative effects of the short QT N588K mutation at 37 degrees C on hERG K+ channel current during ventricular, Purkinje fibre and atrial action potentials: an action potential clamp study. J Physiol Pharmacol 2009; 60:23.
  35. Cordeiro JM, Greene L, Heilmann C, et al. Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle. Am J Physiol Heart Circ Physiol 2004; 286:H1471.
  36. Sah R, Ramirez RJ, Oudit GY, et al. Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (I(to)). J Physiol 2003; 546:5.
  37. Schimpf R, Antzelevitch C, Haghi D, et al. Electromechanical coupling in patients with the short QT syndrome: further insights into the mechanoelectrical hypothesis of the U wave. Heart Rhythm 2008; 5:241.
  38. Bellocq C, van Ginneken AC, Bezzina CR, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 2004; 109:2394.
  39. Priori SG, Pandit SV, Rivolta I, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 2005; 96:800.
  40. Anttonen O, Väänänen H, Junttila J, et al. Electrocardiographic transmural dispersion of repolarization in patients with inherited short QT syndrome. Ann Noninvasive Electrocardiol 2008; 13:295.
  41. Gupta P, Patel C, Patel H, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 2008; 41:567.
  42. Anttonen O, Junttila MJ, Maury P, et al. Differences in twelve-lead electrocardiogram between symptomatic and asymptomatic subjects with short QT interval. Heart Rhythm 2009; 6:267.
  43. Lu LX, Zhou W, Zhang X, et al. Short QT syndrome: a case report and review of literature. Resuscitation 2006; 71:115.
  44. Schimpf R, Bauersfeld U, Gaita F, Wolpert C. Short QT syndrome: successful prevention of sudden cardiac death in an adolescent by implantable cardioverter-defibrillator treatment for primary prophylaxis. Heart Rhythm 2005; 2:416.
  45. Giustetto C, Schimpf R, Mazzanti A, et al. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol 2011; 58:587.
  46. Frea S, Giustetto C, Capriolo M, et al. New echocardiographic insights in short QT syndrome: More than a channelopathy? Heart Rhythm 2015; 12:2096.
  47. Harrell DT, Ashihara T, Ishikawa T, et al. Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome. Int J Cardiol 2015; 190:393.
  48. Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol 2010; 3:401.
  49. Wolpert C, Schimpf R, Giustetto C, et al. Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol 2005; 16:54.
  50. Tülümen E, Giustetto C, Wolpert C, et al. PQ segment depression in patients with short QT syndrome: a novel marker for diagnosing short QT syndrome? Heart Rhythm 2014; 11:1024.
  51. Watanabe H, Makiyama T, Koyama T, et al. High prevalence of early repolarization in short QT syndrome. Heart Rhythm 2010; 7:647.
  52. Antzelevitch C, Yan GX. J wave syndromes. Heart Rhythm 2010; 7:549.
  53. Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm 2011; 8:1308.
  54. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Europace 2015; 17:1601.
  55. Zhang Y, Post WS, Dalal D, et al. QT-interval duration and mortality rate: results from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2011; 171:1727.
  56. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932.
  57. Schimpf R, Wolpert C, Bianchi F, et al. Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery. J Cardiovasc Electrophysiol 2003; 14:1273.
  58. Gaita F, Giustetto C, Bianchi F, et al. Short QT syndrome: pharmacological treatment. J Am Coll Cardiol 2004; 43:1494.
  59. McPate MJ, Duncan RS, Witchel HJ, Hancox JC. Disopyramide is an effective inhibitor of mutant HERG K+ channels involved in variant 1 short QT syndrome. J Mol Cell Cardiol 2006; 41:563.
  60. Mizobuchi M, Enjoji Y, Yamamoto R, et al. Nifekalant and disopyramide in a patient with short QT syndrome: evaluation of pharmacological effects and electrophysiological properties. Pacing Clin Electrophysiol 2008; 31:1229.
  61. El Harchi A, Melgari D, Zhang YH, et al. Action potential clamp and pharmacology of the variant 1 Short QT Syndrome T618I hERG K⁺ channel. PLoS One 2012; 7:e52451.
  62. Hong K, Bjerregaard P, Gussak I, Brugada R. Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. J Cardiovasc Electrophysiol 2005; 16:394.
  63. Villafañe J, Atallah J, Gollob MH, et al. Long-term follow-up of a pediatric cohort with short QT syndrome. J Am Coll Cardiol 2013; 61:1183.
  64. Mazzanti A, Kanthan A, Monteforte N, et al. Novel insight into the natural history of short QT syndrome. J Am Coll Cardiol 2014; 63:1300.