Skip to main content

T-Wave Alternans

Mechanisms, Relevance, and Clinical Implications

  • Chapter
Cardiac Repolarization

Part of the book series: Contemporary Cardiology ((CONCARD))

  • 106 Accesses

Abstract

Cardiovascular disease is the main cause of death in Western countries and account for more than half a million deaths annually in the USA. Sudden cardiac death (SCD) accounts for more than 50% of cardiovascular mortality and its incidence has been estimated as high as 0.1 to 0.2% in the overall population (1). In approx 1/3 of cardiac patients, SCD is the first manifestation of coronary artery disease, and its incidence is increasing proportionally to the number of risk factors (2).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Goldstein S. Sudden death and coronary heart disease. Sudden death and coronary heart disease. Mt. Kisco, NY: Futura Publishing Co., 1974.

    Google Scholar 

  2. Myerburg RJ, Kessler KM, Castellanos A. Sudden cardiac death: epidemiology, transient risk, and intervention assessment. Ann Intern Med 1993;119(12):1187–1197.

    Article  PubMed  CAS  Google Scholar 

  3. Lee TH, Goldman L. The coronary care unit turns 25: historical trends and future directions. Ann Intern Med 1988;108:887–894.

    Article  PubMed  CAS  Google Scholar 

  4. Anonymous. Metoprolol in acute myocardial infarction. Mortality. The MIAMI Trial Research Group. Am J Cardiol 1985;56:15G–22G.

    Google Scholar 

  5. Tanel RE, Triedman JK, Walsh EP, et al. High-rate atrial pacing as an innovative bridging therapy in a neonate with congenital long QT syndrome. J Cardiovasc Electrophysiol 1997;8:812–817.

    Article  PubMed  CAS  Google Scholar 

  6. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 2000;342(26):1937–1945.

    Article  PubMed  CAS  Google Scholar 

  7. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996;335:1933–1940.

    Article  PubMed  CAS  Google Scholar 

  8. Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999;341(25):1882–1890.

    Article  PubMed  CAS  Google Scholar 

  9. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346(12):877–883.

    Article  PubMed  Google Scholar 

  10. Antzelevitch C, Yan GX, Shimizu W, Burashnikov A. Electrical heterogeneity, the ECG, and cardiac arrhythmias. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology. From Cell to Bedside. W.B. Saunders Company, 2000:222–238.

    Google Scholar 

  11. Herring H. Experimentelle Studien an Saugetieren uber das Electrocardiogramm. Z Exper Med 1909;7:363.

    Google Scholar 

  12. Lewis T. Notes upon alternation of the heart. Q J Med 1910;4:141–144.

    Google Scholar 

  13. Kalter HH, Schwartz ML. Electrical alternans. NY State J Medicine 1948;98:1164–1166.

    Google Scholar 

  14. Puletti M, Curione M, Righetti G, Jacobellis G. Alternans of the ST segment and T-wave in acute myocardial infarction. J Electrocardiol 1980;13:297–300.

    Article  PubMed  CAS  Google Scholar 

  15. Salerno JA, Previtali M, Panciroli C, et al. Ventricular arrhythmias during acute myocardial ischaemia in man. The role and significance of R-ST-T alternans and the prevention of ischaemic sudden death by medical treatment. Eur Heart J 1986;7 Suppl A:63–75.

    Article  PubMed  Google Scholar 

  16. Reddy CV, Kiok JP, Khan RG, El Sherif N. Repolarization alternans associated with alcoholism and hypomagnesemia. Am J Cardiol 1984;53(2):390–391.

    Article  PubMed  CAS  Google Scholar 

  17. Shimoni Z, Flatau E, Schiller D, Barzilay E, Kohn D. Electrical alternans of giant U waves with multiple electrolyte deficits. Am J Cardiol 1984;54(7):920–921.

    Article  PubMed  CAS  Google Scholar 

  18. Kleinfeld MJ, Rozanski JJ. Alternans of the ST segment in Prinzmetal’s angina. Circulation 1977;55:574–577.

    Article  PubMed  CAS  Google Scholar 

  19. Cheng TC. Electrical alternans. An association with coronary artery spasm. Arch Intern Med 1983;143:1052–1053.

    Article  PubMed  CAS  Google Scholar 

  20. Platt SB, Vijgen JM, Albrecht P, Van Hare GF, Carlson MD, Rosenbaum DS. Occult T-wave alternans in long QT syndrome. J Cardiovasc Electrophysiol 1996;7:144–148.

    Article  PubMed  CAS  Google Scholar 

  21. Shimizu W, Yamada K, Arakaki Y, Kamiya T, Shimomura K. Monophasic action potential recordings during T-wave alternans in congenital long QT syndrome. Am Heart J 1996;132:699–701.

    Article  PubMed  CAS  Google Scholar 

  22. Burattini L, Zareba W, Rashba EJ, Couderc JP, Konecki J, Moss AJ. ECG features of microvolt T-wave alternans in coronary artery disease and long QT syndrome patients. J Electrocardiol 1998;31 Suppl: 114–120.

    Article  PubMed  Google Scholar 

  23. Adam DR, Smith JM, Akselrod S, Nyberg S, Powell AO, Cohen RJ. Fluctuations in T-wave morphology and susceptibility to ventricular fibrillation. J Electrocardiol 1984;17:209–218.

    Article  PubMed  CAS  Google Scholar 

  24. Smith JM, Clancy EA, Valeri CR, Ruskin JN, Cohen RJ. Electrical alternans and cardiac electrical instability. Circulation 1988;77(1):110–121.

    Article  PubMed  CAS  Google Scholar 

  25. Rosenbaum DS, Jackson LE, Smith JM, Garan H, Ruskin JN, Cohen RJ. Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med 1994;330:235–241.

    Article  PubMed  CAS  Google Scholar 

  26. Pastore JM, Girouard SD, Laurita KR, Akar FG, Rosenbaum DS. Mechanism linking T-wave alternans to the genesis of cardiac fibrillation. Circulation 1999;99:1385–1394.

    Article  PubMed  CAS  Google Scholar 

  27. Pastore JM, Rosenbaum DS. Role of structural barriers in the mechanism of alternans-induced reentry. Circ Res 2000;87(12):1157–1163.

    Article  PubMed  CAS  Google Scholar 

  28. Narayan SM, Smith JM. Differing rate dependence and temporal distribution of repolarization alternans in patients with and without ventricular tachycardia. J Cardiovasc Electrophysiol 1999;10:61–71.

    Article  PubMed  CAS  Google Scholar 

  29. Gold MR, Bloomfield DM, Anderson KP, et al. A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification. J Am Coll Cardiol 2000;36(7):2247–2253.

    Article  PubMed  CAS  Google Scholar 

  30. Hohnloser S, Cohen RJ. T-wave alternans and left ventricular ejection fraction, but not QT variability index, predict appropriate ICD discharge. J Cardiovasc Electrophysiol 1999;10: 626–627.

    Article  PubMed  CAS  Google Scholar 

  31. Hohnloser SH, Klingenheben T, Zabel M, Li YG, Albrecht P, Cohen RJ. T-wave alternans during exercise and atrial pacing in humans. J Cardiovasc Electrophysiol. 1997;8:987–993.

    Article  PubMed  CAS  Google Scholar 

  32. Hohnloser SH, Klingenheben T, Li YG, Zabel M, Peetermans J, Cohen RJ. T-wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers. J Cardiovasc Electrophysiol 1998;9(12):1258–1268.

    Article  PubMed  CAS  Google Scholar 

  33. Klingenheben T, Zabel M, D’ Agostino RB, Cohen RJ, Hohnloser SH. Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure. Lancet 2000;356(9230): 651–652.

    Article  PubMed  CAS  Google Scholar 

  34. Kitamura H, Ohnishi Y, Okajima K, et al. Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy. J Am Coll Cardiol 2002;39(2): 295–300.

    Article  PubMed  Google Scholar 

  35. Loew LM. Mechanisms and principles of volatage-sensitive fluorescence. In: Rosenbaum DS, Jalife J, eds. Optical Mapping of Cardiac Excitation and Arrhythmias. Futura Publishing, 2001:33–46.

    Google Scholar 

  36. Rosenbaum DS, Jalife J, eds. Optical Mapping of Cardiac Excitation and Arrhythmias. New York, NY: Futura Publishing, 2001.

    Google Scholar 

  37. Diehl RR, Linden D, Chalkiadaki A, Diehl A. Cerebrovascular mechanisms in neurocardiogenic syncope with and without postural tachycardia syndrome. J Auton Nery Syst 1999;76(2–3):159–166.

    Article  CAS  Google Scholar 

  38. Akar FG, Laurita KR, Rosenbaum DS. Cellular basis for dispersion of repolarization underlying reentrant arrhythmias. J Electrocardiol 2000;33 Supp1:23–3133 Supp1:23–31.

    Article  PubMed  Google Scholar 

  39. Laurita KR, Girouard SD, Rosenbaum DS. Modulation of ventricular repolarization by a premature stimulus. Role of epicardial dispersion of repolarization kinetics demonstrated by optical mapping of the intact guinea pig heart. Circ Res 1996;79(3):493–503.

    Article  PubMed  CAS  Google Scholar 

  40. Rosenbaum DS, Kaplan DT, Kanai A, et al. Repolarization inhomogeneities in ventricular myocardium change dynamically with abrupt cycle length shortening. Circulation 1991;84(3):1333–1345.

    Article  PubMed  CAS  Google Scholar 

  41. Hirayama Y, Saitoh H, Atarashi H, Hayakawa H. Electrical and mechanical alternans in canine myocardium in vivo. Dependence on intracellular calcium cycling. Circulation 1993;88:2894–2902.

    Article  PubMed  CAS  Google Scholar 

  42. Luo CH, Rudy Y. A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. Circ Res 1991;68:1501–1526.

    Article  PubMed  CAS  Google Scholar 

  43. Fox JJ, McHarg JL, Gilmour RF Jr. Ionic mechanism of electrical alternans. Am J Physiol 2002;282(2):H516-H530.

    Google Scholar 

  44. Nolasco JB, Dahlen RW. A graphic method for the study of alternation in cardiac action potentials. J Appl Physiol 1968;25(2):191–196.

    PubMed  CAS  Google Scholar 

  45. Vinet A, Chialvo DR, Michaels DC, Jalife J. Nonlinear dynamics of rate-dependent activation in models of single cardiac cells. Circ Res 1990;67(6):1510–1524.

    Article  PubMed  CAS  Google Scholar 

  46. Courtemanche M, Glass L, Keener JP. Instabilities of a propagating pulse in a ring of excitable media. Phys Rev Letters 1993;70(14):2182–2185.

    Article  Google Scholar 

  47. Koller ML, Riccio ML, Gilmour RF Jr. Dynamic restitution of action potential duration during electrical alternans and ventricular fibrillation. Am J Physiol 1998;275(5 Pt 2):H1635-H1642.

    Google Scholar 

  48. Qu Z, Garfinkel A, Chen PS, Weiss JN. Mechanisms of discordant alternans and induction of reentry in simulated cardiac tissue. Circulation 2000;102(14):1664–1670.

    Article  PubMed  CAS  Google Scholar 

  49. Riccio ML, Koller ML, Gilmour RF Jr. Electrical restitution and spatiotemporal organization during ventricular fibrillation. Circ Res 1999;84(8):955–963.

    Article  PubMed  CAS  Google Scholar 

  50. Garfinkel A, Kim YH, Voroshilovsky O, et al. Preventing ventricular fibrillation by flattening cardiac restitution. Proc Natl Acad Sci USA 2000;97(11):6061–6066.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. Qu Z, Kil J, Xie F, Garfinkel A, Weiss JN. Scroll wave dynamics in a three-dimensional cardiac tissue model: roles of restitution, thickness, and fiber rotation. Biophys J. 2000;78(6):2761–2775.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  52. Pruvot E, Jacquemet V, Vesin JM, et al. Action potential alternans in a mono-cellular model based on Beeler-Reuter kinetics. In: Virag N, Blanc O, Kappenberger L, eds. Computer Simulation and Experimental Assessment of Cardiac Electrophysiology. Armonk, NY: Futura Publishing, 2001:69–77.

    Google Scholar 

  53. Kurz RW, Mohabir R, Ren XL, Franz MR. Ischaemia induced alternans of action potential duration in the intact-heart: dependence on coronary flow, preload and cycle length. Eur Heart J 1993;14: 1410–1420.

    Article  PubMed  CAS  Google Scholar 

  54. Murphy CF, Lab MJ, Horner SM, Dick DJ, Harrison FG. Regional electromechanical alternans in anesthetized pig hearts: modulation by mechanoelectric feedback. Am J Physiol 1994;267: H1726-H1735.

    Google Scholar 

  55. Euler DE. Cardiac alternans: mechanisms and pathophysiological significance. Cardiovasc Res 1999;42(3):583–590.

    Article  PubMed  CAS  Google Scholar 

  56. Saitoh H, Bailey JC, Surawicz B. Alternans of action potential duration after abrupt shortening of cycle length: differences between dog Purkinje and ventricular muscle fibers. Circ Res 1988;62:1027–1040.

    Article  PubMed  CAS  Google Scholar 

  57. Saitoh H, Bailey JC, Surawicz B. Action potential duration alternans in dog Purkinje and ventricular muscle fibers. Further evidence in support of two different mechanisms. Circulation 1989;80: 1421–1431.

    Article  PubMed  CAS  Google Scholar 

  58. Rubenstein DS, Lipsius SL. Premature beats elicit a phase reversal of mechanoelectrical alternans in cat ventricular myocytes. A possible mechanism for reentrant arrhythmias. Circulation 1995;91:201–214.

    Article  PubMed  CAS  Google Scholar 

  59. Lab MJ, Lee JA. Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle. Circ Res 1990;66(3):585–595.

    Article  PubMed  CAS  Google Scholar 

  60. Hirata Y, Toyama J, Yamada K. Effects of hypoxia or low PH on the alternation of canine ventricular action potentials following an abrupt increase in driving rate. Cardiovasc Res 1980;14(2):108–115.

    Article  PubMed  CAS  Google Scholar 

  61. Allen DG, Lee JA, Smith GL. The consequences of simulated ischaemia on intracellular Ca2+ and tension in isolated ferret ventricular muscle. J Physiol 1989;410:297–323.

    PubMed  CAS  PubMed Central  Google Scholar 

  62. Spear JF, Moore EN. A comparison of alternation in myocardial action potentials and contractility. Am J Physiol 1971;220(6):1708–1716.

    PubMed  CAS  Google Scholar 

  63. Beuckelmann DJ, Wier WG. Mechanism of release of calcium from sarcoplasmic reticulum of guineapig cardiac cells. J Physiol (Lond) 1988;405:233–255.

    CAS  Google Scholar 

  64. Estes NA, Michaud G, Zipes DP, et al. Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias. Am J Cardiol 1997;80:1314–1318.

    Article  PubMed  Google Scholar 

  65. Meissner G. Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. Annu Rev Physiol 1994;56:485–508.

    Article  PubMed  CAS  Google Scholar 

  66. Bassani RA, Bassani JW, Bers DM. Relaxation in ferret ventricular myocytes: unusual interplay among calcium transport systems. J Physiol 1994;476(2):295–308.

    PubMed  CAS  PubMed Central  Google Scholar 

  67. Reeves JP, Hale CC. The stoichiometry of the cardiac sodium-calcium exchange system. J Biol Chem 1984;259(12):7733–7739.

    PubMed  CAS  Google Scholar 

  68. Laurita KR, Singal A, Pastore JM, Rosenbaum DS. Spatial heterogeneity of calcium transients may explain action potential dispersion during T-wave alternans. Circulation 1998;I–187.

    Google Scholar 

  69. Orchard CH, McCall E, Kirby MS, Boyett MR. Mechanical alternans during acidosis in ferret heart muscle. Circ Res 1991;68(1):69–76.

    Article  PubMed  CAS  Google Scholar 

  70. Chudin E, Goldhaber J, Garfinkel A, Weiss J, Kogan B. Intracellular Ca(2+) dynamics and the stability of ventricular tachycardia. Biophys J 1999;77(6):2930–2941.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  71. Huser J, Wang YG, Sheehan KA, Cifuentes F, Lipsius SL, Blatter LA. Functional coupling between glycolysis and excitation-contraction coupling underlies alternans in cat heart cells. J Physiol 2000;524 Pt 3:795–806.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  72. Varro A, Lathrop DA. Sotalol and mexiletine: combination of rate-dependent electrophysiological effects. J Cardiovasc Pharmacol 1990;16(4):557–567.

    Article  PubMed  CAS  Google Scholar 

  73. Lathrop DA, Varro A. The combined electrophysiological effects of lignocaine and sotalol in canine isolated cardiac Purkinje fibres are rate-dependent. Br J Pharmacol 1990;99(1):124–130.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  74. Lathrop DA, Varro A, Schwartz A. Rate-dependent electrophysiological effects of OPC-8212: comparison to sotalol. Eur J Pharmacol 1989;164(3):487–496.

    Article  PubMed  CAS  Google Scholar 

  75. Downar E, Janse MJ, Durrer D. The effect of acute coronary artery occlusion on subepicardial transmemhrane nntentials in the intact porcine heart Circnlatinn 1977;56:217–224.

    CAS  Google Scholar 

  76. Konta T, Ikeda K, Yamaki M, et al. Significance of discordant ST alternans in ventricular fibrillation. Circulation 1990;82:2185–2189.

    Article  PubMed  CAS  Google Scholar 

  77. Kuo CS, Munakata K, Reddy CP, Surawicz B. Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations. Circulation 1983;67:1356–1367.

    Article  PubMed  CAS  Google Scholar 

  78. Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the occurrence of unidirectional block, as studied with multiple microelectrodes. Circ Res 1976;39:168–177.

    Article  PubMed  CAS  Google Scholar 

  79. Watanabe MA, Fenton FH, Evans SJ, Hastings HM, Karma A. Mechanisms for discordant alternans. J Cardiovasc Electrophysiol 2001;12(2):196–206.

    Article  PubMed  CAS  Google Scholar 

  80. Fox JJ, Riccio ML, Hua F, Bodenschatz E, Gilmour RF, Jr. Spatiotemporal transition to conduction block in canine ventricle. Circ Res 2002;90(3):289–296.

    Article  PubMed  CAS  Google Scholar 

  81. Tan RC, Joyner RW. Electrotonic influences on action potentials from isolated ventricular cells. Circ Res 1990;67(5):1071–1081.

    Article  PubMed  CAS  Google Scholar 

  82. Kaufman ES, Mackall JA, Julka B, Drabek C, Rosenbaum DS. Influence of heart rate and sympathetic stimulation on arrhythmogenic T-wave alternans. Am J Physiol 2000;279(3):H1248-H1255.

    Google Scholar 

  83. Sakabe K, Ikeda T, Sakata T, et al. Comparison of T-wave alternans and QT interval dispersion to predict ventricular tachyarrhythmia in patients with dilated cardiomyopathy and without antiarrhythmic drugs: a prospective study. Jpn Heart J 2001;42(4):451–457.

    Article  PubMed  CAS  Google Scholar 

  84. Sakabe K, Ikeda T, Sakata T, et al. Predicting the recurrence of ventricular tachyarrhythmias from T-wave alternans assessed on antiarrhythmic pharmacotherapy: a prospective study in patients with dilated cardiomyopathy. Ann Noninvasive Electrocardiol 2001:6(3):203–208.

    Article  PubMed  CAS  Google Scholar 

  85. Kavesh NG, Shorofsky SR, Sarang SE, Gold MR. The effect of procainamide on T-wave alternans. J Cardiovasc Electrophysiol 1999.10(5).649—654

    Article  PubMed  CAS  Google Scholar 

  86. Ikeda T, Sakata T, Takami M, et al. Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction. A prospective study. J Am Coll Cardiol 2000;35(3):722–730.

    Article  PubMed  CAS  Google Scholar 

  87. Ikeda T, Saito H, Tanno K, et al. T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. Am J Cardiol 2002;89(1):79–82.

    Article  PubMed  Google Scholar 

  88. Tapanainen JM, Still AM, Airaksinen KE, Huikuri HV. Prognostic significance of risk stratifiers of mortality, including T-wave alternans, after acute myocardial infarction: results of a prospective followup study. J Cardiovasc Electrophysiol 2001;12(6):645–652.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Pruvot, E., Rosenbaum, D.S. (2003). T-Wave Alternans. In: Gussak, I., Antzelevitch, C., Hammill, S.C., Shen, WK., Bjerregaard, P. (eds) Cardiac Repolarization. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-362-0_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-362-0_23

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-336-7

  • Online ISBN: 978-1-59259-362-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics