The long QT syndrome: A transatlantic clinical approach to diagnosis and therapy

European Heart Journal

Volumn 34, Issue 40, 2013, Pages 3109-3116

  Schwartz, Peter J ^a,b,c,d,e   Ackerman, Michael J ^f,g  

^a UNIVERSITY OF PAVIA   (Italy)

^b FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^c UNIVERSITY OF CAPE TOWN   (South Africa)

^d STELLENBOSCH UNIVERSITY   (South Africa)

^e KING SAUD UNIVERSITY   (Saudi Arabia)

^f MAYO CLINIC   (United States)

^g MAYO GRADUATE SCHOOL   (United States)

Author keywords

Genetics; Implantable cardioverter defibrillator; Keywords Long QT syndrome; Left cardiac sympathetic denervation; QT interval; Sudden cardiac death

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; FLECAINIDE; MEXILETINE; NADOLOL; PROPRANOLOL; RANOLAZINE; SPIRONOLACTONE;

AUTONOMIC DENERVATION; BRADYCARDIA; CARDIOLOGIST; CLINICAL FEATURE; DIAGNOSTIC ACCURACY; DIAGNOSTIC APPROACH ROUTE; DIAGNOSTIC ERROR; DISEASE SEVERITY; HIGH RISK PATIENT; HUMAN; IMPLANTABLE CARDIOVERTER DEFIBRILLATOR; LEFT CARDIAC SYMPATHETIC DENERVATION; LONG QT SYNDROME; PATIENT COMPLIANCE; PRIORITY JOURNAL; REVIEW; SUDDEN DEATH; TREATMENT INDICATION; TREATMENT OUTCOME;

GENETICS; IMPLANTABLE CARDIOVERTER DEFIBRILLATOR; LEFT CARDIAC SYMPATHETIC DENERVATION; LONG QT SYNDROME; QT INTERVAL; SUDDEN CARDIAC DEATH;

ADRENERGIC BETA-ANTAGONISTS; DEATH, SUDDEN, CARDIAC; DEFIBRILLATORS, IMPLANTABLE; ELECTROCARDIOGRAPHY; GENETIC THERAPY; HUMANS; LONG QT SYNDROME; SYMPATHECTOMY;

EID: 84880064816     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/eht089     Document Type: Review

References (64)

1. Schwartz PJ, Periti M, Malliani A. The long Q-T syndrome. Am Heart J 1975;89: 378-390.
2. Schwartz PJ. Idiopathic long QT syndrome: progress and questions. Am Heart J 1985;109:399-411.
3. Tester DJ, Ackerman MJ. Genetic testing for potentially lethal, highly treatable inherited cardiomyopathies/channelopathies in clinical practice. Circulation 2011; 123:1021-1037.
4. Schwartz PJ, Crotti L, Insolia R. Long QT syndrome: from genetics to management. Circ Arrhythm Electrophysiol 2012;5:868-877.
5. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H, Wilde A, Wolpert C, Zipes DP; Heart Rhythm Society (HRS); European Heart Rhythm Association (EHRA). 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). Europace 2011;13:1077-1109.
6. Taggart NW, Haglund CM, Tester DJ. Diagnostic miscues in congenital long-QT syndrome. Circulation 2007;115:2613-2620.
7. Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, Gabbarini F, Goulene K, Insolia R, Mannarino S, Mosca F, Nespoli L, Rimini A, Rosati E, Salice P, Spazzolini C. Prevalence of the congenital long-QT syndrome. Circulation 2009;120:1761-1767.
8. Moss AJ, Schwartz PJ, Crampton RS, Locati E, Carleen E. The long QT syndrome: a prospective international study. Circulation 1985;71:17-21.
9. Corrado D, Pelliccia A, Heidbuchel H, Sharma S, Link M, Basso C, Biffi A, Buja G, Delise P, Gussac I, Anastasakis A, Borjesson M, Bjørnstad HH, Carrè F, Deligiannis A, Dugmore D, Fagard R, Hoogsteen J, Mellwig KP, Panhuyzen-Goedkoop N, Solberg E, Vanhees L, Drezner J, Estes NA III, Iliceto S, Maron BJ, Peidro R, Schwartz PJ, Stein R, Thiene G, Zeppilli P, McKenna WJ; On behalf of the Sections of Sports Cardiology of the European Association of Cardiovascular Prevention and Rehabilitation; and the Working Group of Myocardial and Pericardial Disease of the European Society of Cardiology. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010;31:243-259.
10. Myerburg RJ, Vetter VL. Electrocardiograms should be included in preparticipation screening of athletes. Circulation 2007;116:2616-2626.
11. Schwartz PJ. Newborn ECG screening to prevent sudden cardiac death. Heart Rhythm 2006;3:1353-1355.
12. Quaglini S, Rognoni C, Spazzolini C, Priori SG, Mannarino S, Schwartz PJ. Costeffectiveness of neonatal ECG screening for the Long QT-Syndrome. Eur Heart J 2006;27:1824-1832.
13. Viskin S, Rosovski U, Sands AJ, Chen E, Kistler PM, Kalman JM, Rodriguez Chavez L, Iturralde Torres P, Cruz F FE, Centurión OA, Fujiki A, Maury P, Chen X, Krahn AD, Roithinger F, Zhang L, Vincent GM, Zeltser D. Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one. Heart Rhythm 2005;2:569-574.
14. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome: an update. Circulation 1993;88:782-784.
15. Schwartz PJ, Crotti L. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation 2011;124:2181-2184.
16. Rautaharju PM, Surawicz B, Gettes LS, Bailey JJ, Childers R, Deal BJ, Gorgels A, Hancock EW, Josephson M, Kligfield P, Kors JA, Macfarlane P, Mason JW, Mirvis DM, Okin P, Pahlm O, van Herpen G, Wagner GS, Wellens H; American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; American College of Cardiology Foundation; Heart Rhythm Society. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation 2009;119:e241-50.
17. Schwartz PJ. Clinical significance of QT prolongation: a personal view. In: Butrous GS, Schwartz PJ (eds), Clinical Aspects of Ventricular Repolarization. London: Farrand Press; 1989, p343-356.
18. Malfatto G, Beria G, Sala S, Bonazzi O, Schwartz PJ. Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome. J Am Coll Cardiol 1994;23:296-301.
19. Schwartz PJ, Malliani A. Electrical alternation of the T wave. Clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long QT syndrome. Am Heart J 1975;89:45-50.
20. Horner JM, Horner MM, Ackerman MJ. The diagnostic utility of recovery phase QTc during treadmill exercise stress testing in the evaluation of long QT syndrome. Heart Rhythm 2011;8:1698-1704.
21. 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.
22. ShimizuW, Noda T, Takaki H, Nagaya N, Satomi K, Kurita T, Suyama K, Aihara N, Sunagawa K, Echigo S, Miyamoto Y, Yoshimasa Y, Nakamura K, Ohe T, Towbin JA, Priori SG, Kamakura S. Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome. Heart Rhythm 2004;1: 276-283.
23. Viskin S, Postema PG, Bhuiyan ZA, Rosso R, Kalman JM, Vohra JK, Guevara-Valdivia ME, Marquez MF, Kogan E, Belhassen B, Glikson M, Strasberg B, Antzelevitch C, Wilde AA. The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. J Am Coll Cardiol 2010;55:1955-1961.
24. Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde A, Ackerman MJ. Genetic testing for long QT syndrome -distinguishing pathogenic mutations from benign variants. Circulation 2009;120:1752-1760.
25. Wilde AA, Ackerman MJ. Exercise extreme caution when calling rare genetic variants novel arrhythmia syndrome-susceptibilty mutations. Heart Rhythm 2010;7: 1883-1885.
26. Moss AJ, Zareba W, Kaufman ES, Gartman E, Peterson DR, Benhorin J, Towbin JA, Keating MT, Priori SG, Schwartz PJ, Vincent GM, Robinson JL, Andrews ML, Feng C, Hall WJ, Medina A, Zhang L, Wang Z. Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-A-go-go-related gene potassium channel. Circulation 2002;105: 794-799.
27. Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, McNitt S. Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation 2007;115:2481-2489.
28. Crotti L, Spazzolini C, Schwartz PJ, Shimizu W, Denjoy I, Schulze-Bahr E, Zaklyazminskaya EV, Swan H, Ackerman MJ, Moss AJ, Wilde AA, Horie M, Brink PA, Insolia R, De Ferrari GM, Crimi G. The common long QT syndrome mutation KCNQ1/A341V causes unusually severe clinical manifestations in patients with different ethnic backgrounds: toward a mutation-specific risk stratification. Circulation 2007;116:2366-2375.
29. Chockalingam P, Crotti L, Girardengo G, Johnson JN, Harris KM, van der Heijden JF, Hauer RNW, Beckmann BM, Spazzolini C, Rordorf R, Rydberg A, Clur SAB, Paed FCP, Fischer M, van den Heuvel F, Kääb S, Blom NA, Ackerman MJ, Schwartz PJ, Wilde AAM. Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. J Am Coll Cardiol 2012;60:2092-2099.
30. Chatrath R, Bell CM, Porter CJ, Ackerman MJ. b-Blocker therapy failures in probands with genotyped long QT syndrome. Pediatric Cardiol 2004;25:459-465.
31. Besana A, Wang DW, George AL Jr, Schwartz PJ. Nadolol block of Nav1.5 does not explain its efficacy in the long QT syndrome. J Cardiovasc Pharmacol 2012;59: 249-253.
32. Moss AJ, ZarebaW, Hall WJ, Schwartz PJ, Crampton RS, Benhorin J, Vincent GM, Locati EH, Priori SG, Napolitano C, Medina A, Zhang L, Robinson JL, Timothy K, Towbin JA, Andrews ML. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2000;101:616-623.
33. Priori SG, Napolitano C, Schwartz PJ, Grillo M, Bloise R, Ronchetti E, Moncalvo C, Tulipani C, Veia A, Bottelli G, Nastoli J. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA 2004;292: 1341-1344.
34. Vincent GM, Schwartz PJ, Denjoy I, Swan H, Bithell C, Spazzolini C, Crotti L, Piippo K, Lupoglazoff JM, Villain E, Priori SG, Napolitano C, Zhang L. High efficacy of beta-blockers in long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of beta-blocker treatment 'failures'. Circulation 2009;119:215-221.
35. 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, Bloise R. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-Threatening arrhythmias. Circulation 2001;103:89-95.
36. Schwartz PJ, Spazzolini C, Crotti L. All LQT3 patients need an ICD. True or false? Heart Rhythm 2009;6:113-120.
37. Schwartz PJ, Priori SG, Cerrone M, Spazzolini C, Odero A, Napolitano C, Bloise R, De Ferrari GM, Klersy C, Moss AJ, Zareba W, Robinson JL, Hall WJ, Brink PA, Toivonen L, Epstein AE, Li C, Hu D. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long QT syndrome. Circulation 2004;109:1826-1833.
38. Collura CA, Johnson JN, Moir C, Ackerman MJ. Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-Assisted thoracic surgery. Heart Rhythm 2009; 6:752-759.
39. Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, Shkolnikova M, Berul CI, Bitner-Glindzicz M, Toivonen L, Horie M, Schulze-Bahr E, Denjoy I. The Jervell and Lange-Nielsen syndrome. Natural history, molecular basis, and clinical outcome. Circulation 2006;113:783-790.
40. Odero A, Bozzani A, De Ferrari GM, Schwartz PJ. Left cardiac sympathetic denervation for the prevention of life-Threatening arrhythmias: the surgical supraclavicular approach to cervicothoracic sympathectomy. Heart Rhythm 2010;7: 1161-1165.
41. Schwartz PJ, Snebold NG, Brown AM. Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold. Am J Cardiol 1976;37: 1034-1040.
42. Schwartz PJ. Cutting nerves and saving lives. Heart Rhythm 2009;6:760-763.
43. Schwartz PJ, Stone HL. Left stellectomy and denervation supersensitivity in conscious dogs. Am J Cardiol 1982;49:1185-1190.
44. Schwartz PJ, Stone HL. Effects of unilateral stellectomy upon cardiac performance during exercise in dogs. Circ Res 1979;44:637-645.
45. Schwartz PJ. Efficacy of left cardiac sympathetic denervation has an unforeseen side effect: medicolegal complications. Heart Rhythm 2010;7:1330-1332.
46. Schwartz PJ, Spazzolini C, Priori SG, Crotti L, Vicentini A, Landolina M, Gasparini M, Wilde AAM, Knops RE, Denjoy I, Toivonen L, Mönnig G, Al-Fayyadh M, Jordaens L, Borggrefe M, Holmgren C, Brugada P, De Roy L, Hohnloser SH, Brink PA. Who are the long-QT syndrome patients who receive an implantable cardioverter defibrillator and what happens to them? Data from the European long-QT syndrome implantable cardioverterdefibrillator (LQTS ICD) Registry. Circulation 2010;122:1272-1282.
47. Horner JM, Kinoshita M, Webster TL, Haglund CM, Friedman PA, Ackerman MJ. Implantable cardioverter defibrillator therapy for congenital long QT syndrome: A single-center experience. Heart Rhythm 2010;7:1616-1622.
48. Schwartz PJ, Priori SG. Long QT syndrome: genotype-phenotype correlations. In: Zipes DP, Jalife J (eds), Cardiac Electrophysiology. From Cell to Bedside, 4th ed. Philadelphia: WB Saunders Co.; 2004, p651-659.
49. Crotti L, Spazzolini C, Porretta AP, Dagradi F, Taravelli E, Petracci B, Vicentini A, Pedrazzini M, La Rovere MT, Vanoli E, Goosen A, Heradien M, Brink PA, George AL Jr, Schwartz PJ. 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 2012;60:2515-2524.
50. Johnson JN, Ackerman MJ. Competitive sports participation in athletes with congenital long QT syndrome. JAMA 2012;308:764-765.
51. Schwartz PJ, Zaza A, Locati E, Moss AJ. Stress and sudden death. The case of the long QT syndrome. Circulation 1991;83(Suppl II):II71-II80.
52. Choi G, Kopplin LJ, Tester DJ, Will ML, Haglund CM, Ackerman MJ. Spectrum and frequency of cardiac channel defects implicated in swimming-Triggered arrhythmia syndromes. Circulation 2004;110:2119-2124.
53. Khositseth A, Tester DJ, Will ML, Bell CM, Ackerman MJ. Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome. Heart Rhythm 2004;1:60-64.
54. Heradien MJ, Goosen A, Crotti L, Durrheim G, Corfield V, Brink PA, Schwartz PJ. Does pregnancy increase cardiac risk for LQT1 patients?. J Am Coll Cardiol 2006; 48:1410-1415.
55. Bennett PB, Yazawa K, Makita N, George AL Jr. Molecular mechanism for an inherited cardiac arrhythmia. Nature 1995;376:683-685.
56. Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantù F, Towbin JA, Keating MT, Hammoude H, Brown AM, Chen LS. 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 1995;92:3381-3386.
57. Ruan Y, Liu N, Bloise R, Napolitano C, Priori SG. Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation 2007;116:1137-1144.
58. Priori SG, Napolitano C, Schwartz PJ, Bloise R, Crotti L, Ronchetti E. The elusive link between LQT3 and Brugada syndrome.: The role of flecainide challenge. Circulation 2000;102:945-947.
59. Benhorin J, Taub R, Goldmit M, Kerem B, Kass RS, Windman I, Medina A. Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long QT syndrome? Circulation 2000;101:1698-1706.
60. Wang DW, Kiyosue T, Sato T, Arita M. Comparison of the effects of class I antiarrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier K+ current of guinea-pig ventricular myocytes. J Mol Cell Cardiol 1996;28: 893-903.
61. Wang DW, Crotti L, Shimizu W, Pedrazzini M, Cantù F, De Filippo P, Kishiki K, Miyazaki A, Ikeda T, Schwartz PJ, George AL Jr. Malignant perinatal variant of long QT syndrome caused by a profoundly dysfunctional cardiac sodium channel. Circ Arrhythm Electrophysiol 2008;1:370-378.
62. Moss AJ, Zareba W, Schwarz KQ, Rosero S, McNitt S, Robinson JL. Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol 2008;19:1289-1293.
63. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D. Risk stratification in the long-QT syndrome. N Engl J Med 2003;348:1866-1874.
64. Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S, Zareba W, Andrews ML, Robinson JL, Locati EH, Ackerman MJ, Benhorin J, Kaufman ES, Napolitano C, Platonov PJ, Priori SG, Qi M, Schwartz PJ, Shimizu W, Towbin JA, Vincent GM, Wilde AAM, Zhang L. Risk for life-Threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. J Am Coll Cardiol 2011;57:51-59.