T wave alternans

T wave alternans (TWA) is a periodic beat-to-beat variation in the amplitude or shape of the T wave in an electrocardiogram (ECG).

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T wave of ECG

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 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 . 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.

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.

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 . 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 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 .

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, ABCD trial, REFINE 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, 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 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.

Links

• 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

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