T wave alternans
TWA was 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 tachycardias.
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. 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.
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.
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, Dr. Joseph Smith, working with Dr. Cohen developed a methodology known as the Spectral Method which allowed measurement of alternans at the level of one microvolt.
Microvolt T wave alternans testing 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. In some cases, the test is equivalent to a more invasive electrophysiology (EP) study.
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 judgments 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.
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.
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, increasing number of studies suggest that the modified moving average may be equivalent or superior with the benefit of also being measurable during a routine Holter exam, since the method doesn't require stationary heart rate in a controlled environment. Also TWA measured using MMA method during stress test is very promising risk stratification method that can be performed during a routine exercise test without the need of a special protocol for maintaining stationary heart rate, or special electrodes.
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). Use of the spectral method for measuring Microvolt T-wave Alternans has been approved for reimbursement by Medicare, as well as major insurers such as Aetna, Cigna, and Humana. Per the National Coverage Determination issued by CMS, "Microvolt T-wave Alternans diagnostic testing is covered for the evaluation of patients at risk for SCD, only when the spectral analysis method is used." 
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.
- 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.
- 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.
- 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.
- Noninvasive Microvolt T-Wave Alternans Test for Selective Targeting of Primary-Prevention ICDs Gets More Trial Support http://www.medscape.com/viewarticle/547941
- 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.
- 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.
- 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
- 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
- "National Coverage Determination (NCD) for Microvolt T-Wave Alternans (MTWA)". Retrieved 21 September 2011.
- "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
- "Monitoring Astronaut's Hearts", Popular Mechanics, April, 2005 http://www.popularmechanics.com/science/health_medicine/1538437.html
- Cambridge Heart Manufacturer of Microvolt T-wave Alternans Systems
- GE Healthcare Manufacturer of Marquette MMA T-wave Alternans Stress Test and Holter Systems
- HRS Webcasts Dr Nieminen Webcast with voice on TWA at HRS 2007
- ISHNE Online Symposium Two interesting educational webcasts on TWA by Dr. Verrier and Dr. Klingenheben
- Medscape Interview Interview with Dr. Exner after publishing REFINE paper