T wave alternans

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T wave alternans (TWA) are periodic beat-to-beat variations in the amplitude of the T wave in an electrocardiogram (ECG).

T wave of ECG
T wave of ECG

TWA were first described in 1908. At that time, only large variations ("macroscopic" TWA) could be detected. Those large TWAs were associated with increased susceptibility to lethal ventricular tachyarrhythmias.

Most modern references to TWA refer to microvolt T-wave alternans (MTWA), a non-invasive heart test that can identify patients who are at increased risk of sudden cardiac death [1][2]. It is most often used in patients who have had myocardial infarctions (heart attacks) or other heart damage to see if they are at high risk of developing a potentially lethal cardiac arrhythmia. Those who are found to be at high risk would therefore benefit from the placement of a defibrillator device which can stop an arrhythmia and save the patient's life.

The TWA test uses an electrocardiogram (ECG) measurement of the heart's electrical conduction. The test looks for the presence of repolarization alternans (T-wave alternans), which is variation in the vector and amplitude of the T-wave component of the EKG. The amount of variation is small, on the order of microvolts, so sensitive digital signal processing techniques are required to detect TWA.

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[edit] Microvolt T-wave Alternans (MTWA)

Microvolt T-Wave Alternans is a variant of T-Wave alternans that detects T-Wave Alternans signals as small as one-millionth of a volt. Microvolt T-wave alternans is defined as an alternation in the morphology of the T-wave in an every other beat or AB-AB pattern. It has long been associated with ventricular arrhythmias and sudden death. First recognized nearly a century ago, visually discernible alternans were linked to the rapid onset of ventricular tachyarrhythmias.

[edit] Historical Development

Research conducted in the early 1980s by Dr. Richard Cohen and his colleagues at MIT explored the idea that visually indiscernible alternans may be equally significant. These efforts established a link between visually imperceptible alternans at the microvolt level and susceptibility to arrhythmias and showed alternans to be a heart rate dependent phenomenon. In addition, they developed a methodology, known as the Spectral Method, which allowed measurement of alternans at the level of one microvolt.

[edit] Clinical Significance

Microvolt T-wave alternans testing acts as a risk stratifier between patients who need implantable cardiac defibrillators (ICDs) and those who do not [3]. Patients who test negative for MTWA are less likely to require an ICD than those who test positive. In some cases, the test is equivalent to a more invasive electrophysiology (EP) study [4].

Multiple prospective clinical trials indicate that patients from broad groups of at risk populations who test MTWA negative will likely live ventricular event-free for 12 to 24 months after their initial MTWA test.

MTWA results are given as positive, negative, or indeterminate. Those with indeterminate results can be tested again. Otherwise, positive and indeterminate results are often lumped together when making clinical judgements about the likelihood of sudden cardiac death. In patients who have a negative (normal) MTWA test the risk of sudden cardiac death is very low. The Negative Predictive Value of MTWA testing has been shown to be 98% accurate for follow-up periods of 12-24 months in various clinical studies. Negative patients should be retested every 12 months as cardiac function can change over time [5].

Patients who test MTWA positive or indeterminate for heart rate or dense ectopy (abnormal) should be referred to an electrophysiologist for further evaluation.

Patients who have an indeterminate test should be retested immediately. Studies indicate that over 50% of patients who initially test as indeterminate, become determinate if retested during the same session.

Relevant clinical studies involving MTWA include the ALPHA trial [6], ABCD trial, REFINE [7]and the MASTER trial (unpublished).

Two methods currently exist to perform MTWA testing -- the spectral analytic method and the modified moving average (MMA) method. Most of the results have come from clinical trials using the spectral analytic method, but limited studies suggest that the modified moving average may be equivalent [8].

[edit] Economics of MTWA

This test is significant for insurance companies because it can potentially save thousands of dollars per patient by reducing the implantation of unnecessary implantable cardiac defibrillators (ICD's) [9]. Use of Microvolt T-wave Alternans has been approved for reimbursement by Medicare, as well as major insurers such as Aetna, Cigna, and Wellpoint.

[edit] MTWA and NASA

In 2004 & 2005, NASA's Glenn Research Center and Cleveland's MetroHealth Medical Center , Case Western Reserve University, teamed to investigate the value of MTWA testing for astronauts both pre- and during space flight. Experiments were performed both on the ground and on NASA's KC-135 aircraft.[10][11]

[edit] References

  1. ^ Chow T, Saghir S, Bartone C, Goebel M, Schneider J, Booth T, Chan PS. Usefulness of microvolt T-wave alternans on predicting outcome in patients with ischemic cardiomyopathy with and without defibrillators.Am J Cardiol. 2007 Aug 15;100(4):598-604. Epub 2007 Jun 28.
  2. ^ Bloomfield DM, Bigger JT, Steinman RC, Namerow PB, Parides MK, Curtis AB, Kaufman ES, Davidenko JM, Shinn TS, Fontaine JM. Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol. 2006 January 17;47(2):456-63. Epub 2005 December 15.
  3. ^ Chow T, Kereiakes DJ, Bartone C, Booth T, Schloss EJ, Waller T, Chung E, Menon S, Nallamothu BK, Chan PS. Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy.J Am Coll Cardiol. 2007 Jan 2;49(1):50-8. Epub 2006 Dec 13.
  4. ^ Noninvasive Microvolt T-Wave Alternans Test for Selective Targeting of Primary-Prevention ICDs Gets More Trial Support http://www.medscape.com/viewarticle/547941
  5. ^ Noninvasive Microvolt T-Wave Alternans Test for Selective Targeting of Primary-Prevention ICDs Gets More Trial Support http://www.medscape.com/viewarticle/547941
  6. ^ Salerno-Uriarte JA, De Ferrari GM, Klersy C, Pedretti RF, Tritto M, Sallusti L, Libero L, Pettinati G, Molon G, Curnis A, Occhetta E, Morandi F, Ferrero P, Accardi F; ALPHA Study Group Investigators. Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy: results of the ALPHA Study. J Am Coll Cardiol. 2007 Nov 6;50(19):1896-904. Epub 2007 Oct 22.
  7. ^ Exner DV, Kavanagh KM, Slawnych MP, Mitchell LB, Ramadan D, Aggarwal SG, Noullett C, Van Schaik A, Mitchell RT, Shibata MA, Gulamhussein S, McMeekin J, Tymchak W, Schnell G, Gillis AM, Sheldon RS, Fick GH, Duff HJ; REFINE Investigators. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol. 2007 Dec 11;50(24):2275-84. Epub 2007 Nov 26.
  8. ^ Nieminen T, Lehtimäki T, Viik J, Lehtinen R, Nikus K, Kööbi T, Niemelä K, Turjanmaa V, Kaiser W, Huhtala H, Verrier RL, Huikuri H, Kähönen M. T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J. 2007 Oct;28(19):2332-7. Epub 2007 Jul 25
  9. ^ Daniel M. Bloomfield; Richard C. Steinman; Pearila B. Namerow; Michael Parides; Jorge Davidenko; Elizabeth S. Kaufman; Timothy Shinn; Anne Curtis; John Fontaine, Douglas Holmes; Andrea Russo; Chuen Tang; J. Thomas Bigger. 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; 110:1885-89
  10. ^ "NASA Teams with MetroHealth To Detect Cardiac Arrhythmias In Astronauts", Space Daily/Space Medicine, Cleveland, OH, Nov 02, 2004 http://www.spacedaily.com/news/spacemedicine-04zzt.html
  11. ^ "Monitoring Astronaut's Hearts", Popular Mechanics, April, 2005 http://www.popularmechanics.com/science/health_medicine/1538437.html
  • Hohnloser SH, Ikeda T, Bloomfield DM, Dabbous OH, Cohen RJ. T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation. The Lancet. 2003;362:125-126.
  • Hohnloser SH, Klingenheben T, Bloomfield D, Dabbous O, Cohen RJ. Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study. J Am Coll Cardiol. 2003;41:2220-4.
  • Grimm W. Quantitative assessment on microvolt T-wave alternans (MTWA) in 204 consecutive patients with congestive heart failure. J Cardiovasc Electrophysiol. 2005 Nov;16(11):1263.
  • Baravelli M, Salerno-Uriarte D, Guzzetti D, Rossi MC, Zoli L, Forzani T, Salerno-Uriarte JA. Predictive significance for sudden death of microvolt-level T wave alternans in New York Heart Association class II congestive heart failure patients: a prospective study. Int J Cardiol. 2005 October 20;105(1):53-7.
  • Costantini O, et al. Patients With a Nonischemic Cardiomyopathy and a Negative T-Wave Alternans Stress Test Are at a Low Risk of Death. AHA 2004 Oral Presentation.
  • Alfred Buxton, Michael O. Sweeney, Elaine Hogan Miller, Marry Otterness, Mark Wathen, Alice Stark. QRS Duration Does not Predict Occurrence of Ventricular Tachyarrhythmias in Primary Prevention Patients With Implantable Cardioverter Defibrillators. ACC 2004, Poster Presentation.
  • Walker ML, Rosenbaum DS. Repolarization alternans: implications for the mechanism and prevention of sudden cardiac death. Cardiovasc Res. 2003;57:599-614.
  • Gold MR, Spencer W. T wave alternans for ventricular arrhythmia risk stratification. Curr Opin Cardiol. 2003;18:1-5.
  • Bloomfield DM, Magnano AR, Parides MK. Comparison of T-wave alternans testing during treadmill and bicycle exercise in patients with congestive heart failure. Am J Cardiol. 2003;91:1493-7, A8.
  • Klingenheben T, Hohnloser SH. Clinical value of T-wave alternans assessment. Card Electrophysiol Rev. 2002;6:323-8.
  • Ikeda T, Kato T, Ozawa Y, Kasamaki Y, Ohnishi Y, Watanabe J, Shimizu H, Tanno K, Saito H. Usefulness of T-Wave Alternans for Effective Prophylactic Therapy in Patients with Prior Myocardial Infarction and Reduced Left Ventricular Ejection Fraction. Circulation. 2002;II:372 (abstract).
  • Ikeda T, Saito H, Tanno K, Shimizu H, Watanabe J, Ohnishi Y, Kasamaki Y, Ozawa Y. T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. Am J Cardiol. 2002;89:79-82.
  • Klingenheben T, Cohen RJ, Bloomfield DM, Hohnloser S. Microvolt T-wave alternans predicts ventricular tachyarrhythmic events in non-ischemic dilated cardiomyopathy patients. Circulation. 2001;104 (suppl II):783 (abstract).
  • 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;356:651-2.
  • Gold MR, Bloomfield DM, Anderson JM, El-Sherif N, Wilber D, Groh WJ, Estes NA, 3rd, Kaufman ES, Greenberg ML, Rosenbaum DS. A Comparison of T-Wave Alternans, Signal Averaged Electrocardiography and Programmed Ventricular Stimulation for Arrhythmia Risk Stratification. J Am Coll Cardiol. 2000;36:2247-53.
  • Cox V, Patel M, Kim J, Liu T, Sivaraman G, Narayan SM. Predicting arrhythmia-free survival using spectral and modified-moving average analyses of T-wave alternans. Pacing Clin Electrophysiol. 2007 Mar;30(3):352-8.
  • Shusterman V, Goldberg A, London B. Upsurge in T-wave alternans and nonalternating repolarization instability precedes spontaneous initiation of ventricular tachyarrhythmias in humans. Circulation. 2006 Jun 27;113(25):2880-7.
  • Exner DV, Kavanagh KM, Slawnych MP, Mitchell, LB, Ramadan D, Aggarwal SG,. et al. Noninvasive Risk assessment Early After a Myocardial Infarction: The REFINE Study. J Am Coll Cardiol. 2007 November 22, 2007;50(24):2275-84

[edit] Links

  • GE Healthcare Manufacturer of Marquette MMA T-wave Alternans Stress Test and Holter Systems