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Sudden Cardiac Death with Apparently Normal Heart: Clinical Implications of Progress in Pathophysiology

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Cardiac Electrophysiology Review

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References

  1. Myerburg RJ, Kessler KM, Castellanous A. Epidemiology of sudden cardiac death: Population characteristics, conditioning risk factors, and dynamic risk factors. In: Spooner PM, Brown AM (eds). Ion Channels in the Cardiovascular System: Function and Dysfunction. Armonk, NY: Futura Publishing, 1994:15-35.

    Google Scholar 

  2. Chugh SS, Kelly KL, Titus JL. Sudden cardiac death with apparently normal heart. Circulation 2000;102(6):649-654.

    Google Scholar 

  3. Consensus Statement of the Joint Steering Committees of the unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United States. Survivors of out-of-hospital cardiac arrest with apparently normal heart—need for definition and standardized clinical evaluation. Circulation 1997;95(1):265-272.

    Google Scholar 

  4. Shen WK, Edwards WD, Hammill SC, Bailey KR, Ballard DJ, Gersh BJ. Sudden unexpected nontraumatic death in 54 young adults: A 30-year population-based study. Am J Cardiol 1995;76(3):148-152.

    Google Scholar 

  5. Luke JL, Helpern M. Sudden unexpected death from natural causes in young adults. A review of 275 consecutive autopsied cases. Arch of Pathol 1968;85(1):10-17.

    Google Scholar 

  6. Kircher T, Nelson J, Burdo H. The autopsy as a measure of accuracy of the death certificate. N Engl J Med 1985;313(20):1263-1269.

    Google Scholar 

  7. Kirschner RH, Eckner FA, Baron RC. The cardiac pathology of sudden, unexplained nocturnal death in Southeast Asian refugees. JAMA 1986;256(19):2700-2705.

    Google Scholar 

  8. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 1988;318(3):129-133.

    Google Scholar 

  9. Priori SG, Barhanin J, Hauer RNW, Haverkamp W, Jongsma HJ, Kleber AG, McKenna WJ, Roden DM, Rudy Y, Schwartz K, Schwartz PJ, Towbin JA, Wilde AM. Genetic and molecular basis of cardiac arrhythmias: Impact on clinical management parts I and II. Circulation 1999;99(4):518-528.

    Google Scholar 

  10. Priori SG, Barhanin J, Hauer RNW, Haverkamp W, Jongsma HJ, Kleber AG, McKenna WJ, Roden DM, Rudy Y, Schwartz K, Schwartz PJ, Towbin, JA, Wilde AM. Genetic and molecular basis of cardiac arrhythmias: Impact on clinical management—Part III. Circulation 1999;99(5):674-681.

    Google Scholar 

  11. Levine SA, Woodworth CR. Congenital deafmutism, prolonged QT interval, syncopal attacks and sudden death. New Engl J Med 1958;259:412-417.

    Google Scholar 

  12. Jervell A, Lange-Nielsen F. Congenital deafmutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J 1957;54:59-68.

    Google Scholar 

  13. Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare dell'eta pediatrica. Clin Pediatr 1963;45:658-683.

    Google Scholar 

  14. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999;97(2):175-187.

    Google Scholar 

  15. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995;80(5):795-803.

    Google Scholar 

  16. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000;102(10):1178-1185.

    Google Scholar 

  17. Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT. Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet 1997;17(3):338-340.

    Google Scholar 

  18. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 1996;12(1):17-23.

    Google Scholar 

  19. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80(5):805-811.

    Google Scholar 

  20. Kaufman E, Priori S, Napolitano C, Schwartz PJ, Iyengar S, Elston RC, Schnell AH, Gorodeski EZ, Rammohan G, Bahhur NO, Connuck D, Verrilli L, Rosenbaum DS, Brown AM. Electrocardiographic prediction of abnormal genotype in congenital long QT syndrome: Experience in 101 related family members. J Cardiovasc Electrophysiol 2001;12(4):455-461.

    Google Scholar 

  21. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992;20(6):1391-1396.

    Google Scholar 

  22. Corrado D, Nava A, Buja G, Martini B, Fasoli G, Oselladore L, Turrini P, Thiene G. Familial cardiomyopathy underlies syndrome of right bundle branch block, ST segment elevation and sudden death. J Am Coll Cardiol 1996;27(2):443-448.

    Google Scholar 

  23. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, Ortiz-Lopez R, Wang Z, Antzelevitch C, O'Brien RE, Schulze-Bahr E, Keating MT, Towbin JA, Wang Q. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998;392(6673):293-296.

    Google Scholar 

  24. Wang DW, Makita N, Kitabatake A, Balser JR, George AL, Jr. Enhanced Na+ channel intermediate inactivation in brugada syndrome. Circ Res 2000;87(8):37e-43e.

    Google Scholar 

  25. Balser JR. Sodium “Channelopathies” and sudden death: Must you be so sensitive? Circ Res 1999;85(9):872-874.

    Google Scholar 

  26. Schott JJ, Alshinawi C, Kyndt F, Probst V, Hoorntje TM, Hulsbeek M, Wilde AA, Escande D, Mannens MM, Le Marec H. Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 1999;23(1):20-21.

    Google Scholar 

  27. Nademanee K, Veerakul G, Nimmannit S, Chaowakul V, Bhuripanyo K, Likittanasombat K, Tunsanga K, Kuasirikul S, Malasit P, Tansupasawadikul S, Tatsanavivat P. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation 1997;96(8):2595-2600.

    Google Scholar 

  28. Brugada R, Brugada J, Antzelevitch C, Kirsch GE, Potenza D, Towbin JA, Brugada P. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101(5):510-515.

    Google Scholar 

  29. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Brignole M, Giordano U, Giovannini T, Menozzi C, Bloise R, Crotti L, Terreni L, Schwartz PJ. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation 2000;102(20):2509-2515.

    Google Scholar 

  30. Takenaka S, Kusano KF, Hisamatsu K, Nagase S, Nakamura K, Morita H, Matsubara H, Emori T, Ohe T. Relatively benign clinical course in asymptomatic patients with brugada-type electrocardiogram without family history of sudden death. J Cardiovasc Electrophysiol 2001;12(1):2-6.

    Google Scholar 

  31. 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(9):945-947.

    Google Scholar 

  32. Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R, Shoda M, Toyoshima Y, Hosoda S. Idiopathic ventricular fibrillation induced with vagal activity in patients without obvious heart disease. Circulation 1997;95(9):2277-2285.

    Google Scholar 

  33. Belhassen B, Viskin S, Fish R, Glick A, Setbon I, Eldar M. Effects of electrophysiologic-guided therapy with Class IA antiarrhythmic drugs on the long-term outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome. J Cardiovasc Electrophysiol 1999;10(10):1301-1312.

    Google Scholar 

  34. Peters RH, Wever EF, Hauer RN, Robles de Medina EO. Low prevalence of coronary artery spasm in patients with normal coronary angiograms and unexplained ventricular fibrillation. Eur Heart J 1998;19(7):1070-1074.

    Google Scholar 

  35. Fellows CL, Weaver WD, Greene HL. Cardiac arrest associated with coronary artery spasm. Am J Cardiol 1987;60(16):1397-1399.

    Google Scholar 

  36. Myerburg RJ, Kessler KM, Mallon SM, Cox MM, deMarchena E, Interian A Jr, Castellanos A. Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronaryartery spasm. N Engl J Med 1992;326(22):1451-1455.

    Google Scholar 

  37. Yamaguchi T. Role of electrophysiologic testing and coronary spasm provocation test in survivors of cardiac arrest. Jpn Circ J 1992;56(4):343-351.

    Google Scholar 

  38. Igarashi Y, Tamura Y, Suzuki K, Tanabe Y, Tamura M, Yamaguchi T, Oshima M, Sakai K, Yamazoe M, Aizawa Y. High prevalence of coronary artery spasm in survivors of cardiac arrest with no apparent heart disease. Jpn Heart J 1992;33(5):653-663.

    Google Scholar 

  39. Jenq RR, Chugh SS, Greenberg GM, McAnulty JH. Sudden death from coronary vasospasm: Persistent angina predicts recurrence. 2001 (In Submission).

  40. Bertrand ME, LaBlanche JM, Tilmant PY, Thieuleux FA, Delforge MR, Carre AG, Asseman P, Berzin B, Liberasa C, Laurent JM. Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation 1982;65(7):1299-1306.

    Google Scholar 

  41. Walling A, Waters DD, Miller DD, Roy D, Pelletier GB, Theroux P. Long-term prognosis of patients with variant angina. Circulation 1987;76(5):990-997.

    Google Scholar 

  42. Woosley R. International registry for drug-induced arrhythmias. 2001, www.Torsades.org.

  43. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: Clinical impact. Circulation 1999;99(4):529-533.

    Google Scholar 

  44. Viskin S, Belhassen B. Polymorphic ventricular tachyarrhythmias in the absence of organic heart disease: Classification, differential diagnosis, and implications for therapy. Prog Cardiovasc Dis 1998;41(1):17-34.

    Google Scholar 

  45. Wellens HJ, Lemery R, Smeets JL, Brugada P, Gorgels AP, Cheriex EC, de Zwaan C. Sudden arrhythmic death without overt heart disease. Circulation 1992;85(Suppl I):I92-I97.

    Google Scholar 

  46. Tung RT, Shen WK, Hammill SC, Gersh BJ. Idiopathic ventricular fibrillation in out-of-hospital cardiac arrest survivors. Pacing clin electrophysiol 1994;17(8):1405-1412.

    Google Scholar 

  47. Meissner MD, Lehmann MH, Steinman RT, Mosteller RD, Akhtar M, Calkins H, Cannom DS, Epstein AE, Fogoros RN, Liem LB. Ventricular fibrillation in patients without significant structural heart disease: A multicenter experience with implantable cardioverter-defibrillator therapy. J Am Coll Cardiol 1993;21(6):1406-1412.

    Google Scholar 

  48. Leenhardt A, Glaser E, Burguera M, Nurnberg M, Maison-Blanche P, Coumel P. Short-coupled variant of torsade de pointes. A new electrocardiographic entity in the spectrum of idiopathic ventricular tachyarrhythmias. Circulation 1994;89(1):206-215.

    Google Scholar 

  49. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P. Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation 1995;91(5):1512-1519.

    Google Scholar 

  50. Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino VV, Danieli GA. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 2001;103(2):196-200.

    Google Scholar 

  51. Hennersdorf MG, Strauer BE. Arterial hypertension and cardiac arrhythmias. J Hypertens 2001;19(2):167-177.

    Google Scholar 

  52. Bikkina M, Larson MG, Levy D. Asymptomatic ventricular arrhythmias and mortality risk in subjects with left ventricular hypertrophy. J Am Coll Cardiol 1993;22(4):1111-1116.

    Google Scholar 

  53. Wilde AAM. Hypertrophy and Arrhythmias. In: van der Wall EE, et al. (eds). Left Ventricular Hypertrophy. Dordrecht, The Netherlands: Kluwer Academic Publishers, 1999.

    Google Scholar 

  54. John B, Chugh SS, Okouchi M, McAnulty JH, Titus JL. Significant incidence of unexplained myocardial interstitial fibrosis: Can it explain sudden cardiac death? PACE 2001;24(4(II)):715.

    Google Scholar 

  55. Cheng TO, Chugh SS, Kelly KL, Titus JL. Sudden cardiac death in mitral valve prolapse response. Circulation 2001;103(16):e88.

    Google Scholar 

  56. Pocock WA, Bosman CK, Chesler E, Barlow JB, Edwards JE. Sudden death in primary mitral valve prolapse. Am Heart J 1984;107(2):378-382.

    Google Scholar 

  57. Kligfield P, Hochreiter C, Niles N, Devereux RB, Borer JS. Relation of sudden death in pure mitral regurgitation, with and without mitral valve prolapse, to repetitive ventricular arrhythmias and right and left ventricular ejection fractions. Am J Cardiol 1987;60(4):397-399.

    Google Scholar 

  58. Hauser WA, Hesdorffer DC. Epilepsy: Frequency, causes and consequences. New York, NY: Demos, 1990.

    Google Scholar 

  59. Nilsson L, Farahmand BY, Persson PG, Thiblin I, Tomson T. Risk factors for sudden unexpected death in epilepsy: A case-control study. Lancet 1999;353(9156):888-893.

    Google Scholar 

  60. Nilsson L, Tomson T, Farahmand BY, Diwan V, Persson PG. Cause-specific mortality in epilepsy: A cohort study of more than 9,000 patients once hospitalized for epilepsy. Epilepsia 1997;38(10):1062-1068.

    Google Scholar 

  61. Tennis P, Cole TB, Annegers JF, Leestma JE, McNutt M, Rajput A. Cohort study of incidence of sudden unexplained death in persons with seizure disorder treated with antiepileptic drugs in Saskatchewan, Canada. Epilepsia 1995;36(1):29-36.

    Google Scholar 

  62. Walczak TS, Leppik IE, D'Amelio M, Rarick J, So E, Ahman P, Ruggles K, Cascino GD, Annegers JF, Hauser WA. Incidence and risk factors in sudden unexpected death in epilepsy: A prospective cohort study. Neurology 2001;56(4):519-525.

    Google Scholar 

  63. Natelson BH, Suarez RV, Terrence CF, Turizo R. Patients with epilepsy who die suddenly have cardiac disease. Arch Neurol 1998;55:857-860.

    Google Scholar 

  64. Lathers CM, Schraeder PL. Autonomic dysfunction in epilepsy: Characterization of autonomic cardiac neural discharge associated with pentylenetetrazol-induced epileptogenic activity. Epilepsia 1982;23(6):633-647.

    Google Scholar 

  65. Lathers CM, Schraeder PL. Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity. J Clin Pharmacol 1987;27(5):346-356.

    Google Scholar 

  66. Sjostrom LV. Mortality of severely obese subjects. American Journal of Clinical Nutrition 1992;55(Suppl II):516S-523S.

    Google Scholar 

  67. Lavie CJ, Amodeo C, Ventura HO, Messerli FH. Left atrial abnormalities indicating diastolic ventricular dysfunction in cardiopathy of obesity. Chest 1987;92(6):1042-1046.

    Google Scholar 

  68. Duflou J, Virmani R, Rabin I, Burke A, Farb A, Smialek J. Sudden death as a result of heart disease in morbid obesity. Am Heart J 1995;130(2):306-313.

    Google Scholar 

  69. Messerli FH, Nunez BD, Ventura HO, Snyder DW. Overweight and sudden death. Increased ventricular ectopy in cardiopathy of obesity. Arch Int Med 1987;147(10):1725-1728.

    Google Scholar 

  70. Warnes CA, Roberts WC. The heart in massive (more than 300 pounds or 136 kilograms) obesity: Analysis of 12 patients studied at necropsy. Am J Cardiol 1984;54(8):1087-1091.

    Google Scholar 

  71. Petretta M, Bonaduce D, de Filippo E, Mureddu GF, Scalfi L, Marciano F, Bianchi V, Salemme L, de Simone G, Contaldo F. Assessment of cardiac autonomic control by heart period variability in patients with early-onset familial obesity. Eur J Clin Invest 1995;25(11):826-832.

    Google Scholar 

  72. Zheutlin TA, Steinman RT, Mattioni TA, Kehoe RF. Long-term arrhythmic outcome in survivors of ventricular fibrillation with absence ofinducible ventricular tachycardia. Am J Cardiol 1988;62(17):1213-1217.

    Google Scholar 

  73. Lloyd EA, Hauer RN, Zipes DP, Heger JJ, Prystowsky EN. Syncope and ventricular tachycardia in patients with ventricular preexcitation. Am J Cardiol 1983;52(1):79-82.

    Google Scholar 

  74. Klein GJ, Bashore TM, Sellers TD, Pritchett EL, Smith WM, Gallagher JJ. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. N Eng J Med 1979;301(20):1080-1085.

    Google Scholar 

  75. Hays LJ, Lerman BB, DiMarco JP. Nonventricular arrhythmias as precursors of ventricular fibrillation in patients with out-of-hospital cardiac arrest. Am Heart J 1989;118(1):53-57.

    Google Scholar 

  76. Benditt DG, Pritchett LC, Smith WM, Wallace AG, Gallagher JJ. Characteristics of atrioventricular conduction and the spectrum of arrhythmias in lown-ganong-levine syndrome. Circulation 1978;57(3):454-465.

    Google Scholar 

  77. Wang YS, Scheinman MM, Chien WW, Cohen TJ, Lesh MD, Griffin JC. Patients with supraventricular tachycardia presenting with aborted sudden death: Incidence, mechanism and long-term follow-up. J Am Coll Cardiol 1991;18(7):1711-1719.

    Google Scholar 

  78. Spooner PM, Albert C, Benjamin EJ, Boineau R, Elston RC, George AL, Jr, Jouven X, Kuller LH, MacCluer JW, Marban E, Muller JE, Schwartz PJ, Siscovick DS, Tracy RP, Zareba W, Zipes DP. Sudden cardiac death, genes, and arrhythmogenesis: Consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, Part I. Circulation 2001;103(19):2361-2364.

    Google Scholar 

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    Sumeet S. Chugh

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Chugh, S.S. Sudden Cardiac Death with Apparently Normal Heart: Clinical Implications of Progress in Pathophysiology. Card Electrophysiol Rev 5, 394–402 (2001). https://doi.org/10.1023/A:1013254132689

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