T wave alternans

T-wave alternans (TWA) is a non-invasive test of the heart that is used to identify patients who are at increased risk of sudden cardiac death. 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 cardial 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 (EKG) 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.

TWA were first described in 1908, and at that time when sensitive digital techniques were not available, only large variation ("macroscopic" TWA) could be detected. Those large TWAs were associated with increased susceptibility to lethal ventricular tachyarrhythmias.

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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.

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.

Two methods currently exist to perform digital analsyis MTWA testing -- a spectral analytic method and a modified moving average (MMA) method.

Clinical Significance

MTWA is significant in the clinical context because it acts as a risk stratifier between patients who need implantable cardiac defibrillators (ICDs) and those who do not. Patients who test negative for MTWA are less likely to require an ICD than those who test positive.

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.

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.

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.

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. Use of Microvolt T-wave Alternans has been approved for reimbursement by Medicare, as well as major insurers such as Aetna, Cigna, and Wellpoint.

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.^[1][2]

References

• T Wave Alternans And Ventricular Tachyarrhythmia Risk Stratification: A Review by Masahiko Takagi and Junichi Yoshikawa in Indian Pacing Electrophysiol. J. 2003;3(2):67

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Nieminen T, Lehtimaki T, Viik J, Lehtinen R, Nikus K, Koobi T, et al. T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J. 2007 Jul 25.

1. ^ "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
2. ^ "Monitoring Astronaut's Hearts", Popular Mechanics, April, 2005 http://www.popularmechanics.com/science/health_medicine/1538437.html

Links

• Cambrdige Heart Manufacturer of Microvolt T-wave Alternans Systems

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