Heart Rhythm
Volume 6, Issue 3, Supplement , Pages S22-S28 , March 2009

Explaining the clinical manifestations of T wave alternans in patients at risk for sudden cardiac death

  • Michael J. Cutler, DO, PhD
    • ,
  • David S. Rosenbaum, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. David S. Rosenbaum, Case Western Reserve University, Heart and Vascular Research Center, 2500 MetroHealth Drive, Hamann 330, Cleveland, Ohio 44109-1998

References 

  1. Narayan SM. T-wave alternans and the susceptibility to ventricular arrhythmias. J Am Coll Cardiol. 2006;47:269–281
  2. Rosenbaum DS, Jackson LE, Smith JM, et al. Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med. 1994;330:235–241
  3. Hering HE. Experimentelle studien an Saugertherien uber das elektrocardiogramm (II. Mittheilung). Z Exp Pathol Ther. 1910;7:363–378
  4. Lewis T. Notes upon alternation of the heart. Q J Med. 1910;4:141–144
  5. Bloomfield DM, Steinman RC, Namerow PB, et al. Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: a solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II conundrum. Circulation. 2004;110:1885–1889
  6. Walker ML, Rosenbaum DS. Repolarization alternans: implications for the mechanism and prevention of sudden cardiac death. Cardiovasc Res. 2003;57:599–614
  7. Smith JM, Cohen RJ. Simple finite-element model accounts for wide range of ventricular dysrhythmias. Proc Nat Acad Sci USA. 1984;81:233–237
  8. Hoffman BF, Suckling EE. Effect of heart rate on cardiac membrane potentials and unipolar electrogram. Am J Physiol. 1954;179:123–130
  9. Kleinfeld M, Stein E, Magin J. Electrical alternans in single ventricular fibers of the frog heart. Am J Physiol. 1956;187:139–142
  10. Pastore JM, Girouard SD, Laurita KR, et al. Mechanism linking T-wave alternans to the genesis of cardiac fibrillation. Circulation. 1999;99:1385–1394
  11. Cohen I, Giles W, Noble D. Cellular basis for the T-wave of the electrocardiogram. Nature. 1976;262:657–661
  12. Laurita KR, Katra R, Wible B, et al. Transmural heterogeneity of calcium handling in canine. Circ Res. 2003;92:668–675
  13. Wan X, Laurita KR, Pruvot E, et al. Molecular correlates of repolarization alternans in cardiac myocytes. J Mol Cell Cardiol. 2005;39:419–428
  14. Hohnloser SH, Klingenheben T, Bloomfield D, et al. Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study. J J Am Coll Cardiol. 2003;41:2220–2224
  15. Kaufman ES, Mackall JA, Julka B, et al. Influence of heart rate and sympathetic stimulation on arrhythmogenic T wave alternans. Am J Physiol Heart Circ Physiol. 2000;279:H1248–H1255
  16. Fox JJ, McHarg JL, Gilmour RF. Ionic mechanism of electrical alternans. Am J Physiol Heart Circ Physiol. 2002;282:H516–H530
  17. Qu Z, Garfinkel A, Chen P, et al. Mechanisms of discordant alternans and induction of reentry in simulated cardiac tissue. Circulation. 2000;102:1664–1670
  18. Watanabe MA, Fenton FH, Evans SJ, et al. Mechanisms for discordant alternans. J Cardiovasc Electrophysiol. 2001;12:196–206
  19. Garfinkel A, Kim YH, Voroshilovsky O, et al. Preventing ventricular fibrillation by flattening cardiac restitution. Proc Natl Acad Sci USA. 2000;97:6061–6066
  20. Pruvot EJ, Katra RP, Rosenbaum DS, et al. Role of calcium cycling versus restitution in the mechanism of repolarization alternans. Circ Res. 2004;94:1083–1090
  21. Goldhaber JI, Xie LH, Duong T, et al. Action potential duration restitution and alternans in rabbit ventricular myocytes: the key role of intracellular calcium cycling. Circ Res. 2005;96:459–466
  22. Taggart P, Sutton PMI, Boyett MR, et al. Human ventricular action potential duration during short and long cycles—rapid modulation by ischemia. Circulation. 1996;94:2526–2534
  23. Chow T, Gursoy S, Onufer JR, et al. The MASTER trial investigators: clinical value of repeating indeterminate microvolt T-wave alternans tests. J Am Coll Cardiol. 2005;45:93A;(abstr)
  24. Traube L. Ein Fall von Pulsus Bigeminus nebst Bemerkungen uber die Leberschwellungen bei Klappenfehlern und uber acute Leberatrophie. Berlin Klin Wochenschr. 1872;9:185–188
  25. Hirata Y, Kodama I, Iwamura N, et al. Effects of verapamil on canine Purkinje fibers and ventricular muscle fibers with particular reference to the alternation of action potential duration after a sudden increase in driving rate. Cardiovasc Res. 1979;13:1–8
  26. Saitoh H, Bailey J, 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
  27. Saitoh H, Bailey J, Surawicz B. Action potential duration alternans in dog Purkinje and ventricular muscle fibers. Circulation. 1989;80:1421–1431
  28. Chudin E, Goldhaber JI, Weiss J, et al. Intracellular Ca2 dynamics and the stability of ventricular tachycardia. Biophys J. 1999;77:2930–2941
  29. Diaz ME, O'Neill SC, Eisner DA. Sarcoplasmic reticulum calcium content fluctuation is the key to cardiac alternans. Circ Res. 2004;94:650–656
  30. Picht E, DeSantiago J, Blatter LA, et al. Cardiac alternans do not rely on diastolic sarcoplasmic reticulum calcium content fluctuations. Circ Res. 2006;99:740–748
  31. Xie LH, Sato D, Garfinkel A, et al. Intracellular Ca alternans: coordinated regulation by sarcoplasmic reticulum release, uptake, and leak. Biophys J. 2008;95:3100–3110
  32. Weiss JN, Karma A, Shiferaw Y, et al. From pulsus to pulseless: the saga of cardiac alternans. Circ Res. 2006;98:1244–1253
  33. Hüser J, Wang YG, Sheehan KA, et al. Functional coupling between glycolysis and excitation-contraction coupling underlies alternans in cat heart cells. J Physiol (Lond). 2000;524:795–806
  34. Walker ML, Wan X, Kirsch GE, et al. Hysteresis effect implicates calcium cycling as a mechanism of repolarization alternans. Circulation. 2003;108:2704–2709
  35. 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 Q-T syndrome. Am Heart J. 1975;89:45–50
  36. Costantini O, Hohnloser SH, Kirk MM, et al. The Alternans Before Cardioverter Defibrillator (ABCD) trial: strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention. J Am Coll Cardiol. 2008;in press
  37. Hohnloser SH, Klingenheben T, Li YG, et al. T wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers. J Cardiovasc Electrophysiol. 1998;9:1258–1268
  38. Poelzing S, Akar FG, Baron E, et al. Heterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall. Am J Physiol Heart Circ Physiol. 2004;286:H2001–H2009
  39. Pastore JM, Rosenbaum DS. Role of structural barriers in the mechanism of alternans-induced reentry. Circ Res. 2000;87:1157–1163
  40. Shimizu W, Antzelevitch C. Cellular and ionic basis for T-wave alternans under long-QT conditions. Circulation. 1999;99:1499–1507
  41. The Cardiac Arrhythmia Suppression Trial (CAST) investigators: preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406–412
  42. Kavesh NG, Shorofsky SR, Sarang SE, et al. The effect of procainamide on T wave alternans. J Cardiovasc Electrophysiol. 1999;10:649–654
  43. Tachibana H, Yamaki M, Kubota I, et al. Intracoronary flecainide induces ST alternans and reentrant arrhythmia on intact canine heart—a role of 4-aminopyridine-sensitive current. Circulation. 1999;99:1637–1643
  44. Tada T, Kusano KF, Nagase S, et al. Clinical significance of macroscopic T-wave alternans after sodium channel blocker administration in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2008;19:56–61
  45. Klingenheben T, Grönefeld G, Li YG, et al. Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans—results of a prospective, double-blind, randomized study. J Am Coll Cardiol. 2001;38:2013–2019
  46. Rashba EJ, Cooklin M, MacMurdy K, et al. Effects of selective autonomic blockade on T-wave alternans in humans. Circulation. 2002;105:837–842
  47. Komiya N, Seto S, Nakao K, Yano K. The influence of beta-adrenergic agonists and antagonists on T-wave alternans in patients with and without ventricular tachyarrhythmia. Pacing Clin Electrophysiol. 2005;28:680–684
  48. Hashimoto H, Suzuki K, Miyake S, et al. Effects of calcium antagonists on the electrical alternans of the ST segment and on associated mechanical alternans during acute coronary occlusion in dogs. Circulation. 1983;68:667–672
  49. Hayakawa T, Nagamoto Y, Ninomiya K, et al. Effects of heart rate and diltiazem hydrocholoride on alternans of ST segment elevation and ventricular arrhythmia during acute myocardial ischaemia in dogs. Cardiovasc Res. 1989;23:520–528
  50. Groh WJ, Shinn TS, Engelstein EE, et al. Amiodarone reduces the prevalence of T wave alternans in a population with ventricular tachyarrhythmias. J Cardiovasc Electrophysiol. 1999;10:1335–1339
  51. Kaszala K, Kenigsberg DN, Krishnan SC. Drug-induced T wave alternans. J Cardiovasc Electrophysiol. 2006;17:332
  52. Tan HL, Wilde AAM. T wave alternans after sotalol: evidence for increased sensitivity to sotalol after conversion from atrial fibrillation to sinus rhythm. Heart. 1998;80:303–306
  53. Tomcsányi J, Somlói M, Horváth L. Amiodarone-induced giant T wave alternans hastens proarrhythmic response. J Cardiovasc Electrophysiol. 2002;13:629

 This study was supported by National Institutes of Health grant R01-HL54807 (to David Rosenbaum, MD) and Fellowship Awards from the Heart Rhythm Society and NIH National Research Service Award (to Michael Cutler). Dr. David Rosenbaum receives research support from CardioDx and is a consultant to Cambridge Heart Inc. Dr. Michael Cutler has no potential conflicts of interest.

PII: S1547-5271(08)00974-0

doi: 10.1016/j.hrthm.2008.10.007

Heart Rhythm
Volume 6, Issue 3, Supplement , Pages S22-S28 , March 2009

Article Tools

* Image Usage & Resolution