This document addresses microvolt T-wave alternans (MTWA), a noninvasive electrophysiologic study of the heart that measures beat-to-beat variability in the amplitude of the T-wave. MTWA has been proposed as a risk stratification tool to identify patients at high risk of ventricular arrhythmias and sudden cardiac death (SCD) who would be most likely to benefit from an implantable cardioverter-defibrillator (ICD). 

Note: Please see the following related documents for additional information:

• MED.00074 Computer Analysis of Electrocardiography (ECG)
• SURG.00033 Implantable Cardioverter-Defibrillator (ICD)

Not Medically Necessary:

Microvolt T-wave alternans is considered not medically necessary as a risk stratification tool to identify patients at high risk of ventricular arrhythmias and sudden cardiac death who would be most likely to benefit from an implantable cardioverter-defibrillator (ICD).

Investigational and Not Medically Necessary:

Microvolt T-wave alternans is considered investigational and not medically necessary for all other indications not listed.

Implantable cardioverter-defibrillators (ICDs) have had a major impact on the treatment of ventricular tachyarrhythmias (VT).  ICDs were initially used to treat patients who had survived cardiac arrest or an episode of documented sustained VT. However, the majority of patients who die from sudden cardiac death (SCD) have not had such a prior cardiac event.

Historically, the invasive electrophysiologic study (EPS) was the primary diagnostic tool for risk stratification and selection of ICDs for individual patients. In 2000, the Multi-Center Unsustained Tachycardia Trial (MUSTT) demonstrated that, in patients with a prior myocardial infarction, left ventricular ejection fraction (LVEF) ≤ 0.40, and unsustained ventricular tachycardia, EPS was a poor predictor of future sustained ventricular arrhythmic events (Buxton, 2000).

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II, 2002) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT, 2005) primary prevention trials were the two pivotal studies that established the utility of ICD therapy for the primary prevention of SCD in patients without a history of prior sustained VT.  MADIT II addressed ICD use in patients with prior myocardial infarction and LVEF ≤ 0.30. SCD-HeFT addressed ICD therapy in patients with LVEF ≤ 0.35 with New York Heart Association (NYHA) class II or III heart failure on the basis of either ischemic or non-ischemic cardiomyopathy.

Although the absolute reductions in annual mortality in the MADIT II (4.0%) and SCD-HeFT (2.5%) trials were modest, these studies led the Centers for Medicare and Medicaid Services (CMS) to approve Medicare coverage for ICD therapy for patients meeting criteria established in these trials. While the validity of the ICD prophylaxis trials has been established, there is a need for better risk stratification to target therapy given the inconvenience, risks, and resource implications of implanting ICDs in all patients who meet the MADIT II or SCD-HeFT criteria. Studies of MTWA have focused on the capability of this test to predict the risk of fatal arrhythmias and SCD in patients with a history of myocardial infarction, congestive heart failure, or cardiomyopathy. These high risk patients may be treated with drugs to suppress arrhythmias or undergo implantation of an ICD. A positive MTWA test result is one of many risk factors that have been investigated for identifying candidates for primary prevention with an ICD; others include LVEF, arrhythmias detected on Holter monitor, electrophysiologic studies, heart rate variability, baroreceptor sensitivity and signal-averaged electrocardiography.

In 2003, CMS conducted a subgroup analysis of MADIT II data that looked at the impact of QRS complex duration on patient outcomes. Based on this analysis, CMS announced its intent to limit coverage of ICDs to patients meeting the criteria for the MADIT-II trial with a QRS duration greater than 120 ms, thereby cutting member eligibility by one-third. This strategy was criticized by those who pointed out the hazards of post-hoc subgroup analysis, resulting in CMS lifting this restriction in January 2005. In partial response to this planned restriction, Bloomfield (2004) compared the predictive value of MTWA with QRS duration in patients who would meet the MADIT II criteria. The study population was drawn from a multi-institutional epidemiologic study that examined the prognostic significance of MTWA in patients with left ventricular dysfunction. Of the 549 available patients in the study, 177 also met the MADIT II criteria (prior MI, LVEF < 0.30). This subgroup formed the study group. The mean patient follow-up was 20 months; the primary outcome was all-cause mortality. The two-year mortality rate in patients with an abnormal MTWA test was 17.8%, compared with 3.8% in those with a normal MTWA study. In contrast, the mortality rate for patients with a QRS duration of greater than 120 ms was not significantly different from those with a normal QRS interval. The authors of this trial concluded that the MTWA is a superior risk predictor than the QRS interval. The authors also proposed that a normal MTWA test might be used to deselect patients for an ICD who would otherwise meet the criteria established by the results of the MADIT II trial. These and other observational studies suggested that abnormal MTWA results were an independent risk factor for ventricular arrhythmias and thus could be used to refine patient selection criteria for ICD implantation as a primary preventive therapy (Chow, 2006; Salerno-Uriate, 2007). The initial determination that a MTWA test was medically necessary for patient selection for ICD placement was based in part on these trial results.

However, several recent studies have challenged this role of MTWA. For example, Cantillon and colleagues (2007) prospectively evaluated the effectiveness of MTWA in predicting arrhythmia-free survival and all-cause mortality in patients with LV dysfunction. From a population of patients referred for evaluation of syncope, nonsustained ventricular tachycardia (NSVT), or both, 286 patients with an LVEF of ≤ 0.35 underwent EPS and MTWA assessment. Positive and indeterminate MTWA results were grouped as non-negative. Patients were followed for a mean of 38 ± 11 months. The authors reported there was no significant difference between the MTWA-negative (n=90; 31%) and non-negative (n= 196; 69%) groups with respect to ICD implant rates (54% vs. 64%, respectively; p=0.95) or etiology of cardiomyopathy ischemia (73% vs. 76%; p=0.71). On multivariate analysis, MTWA was a significant predictor of the primary end point (HR of 2.37, 95% CI 1.49 to 3.81; p<0.01), where EPS was a less effective predictor of arrhythmia-free survival (HR 1.27, 95% CI 0.88 to 1.83; p=0.21) and all-cause mortality. The MTWA-negative patients had improved 2-year arrhythmia-free survival compared with MTWA non-negative patients (81% vs. 66%; p<0.0001). In patients with ischemic heart disease, the arrhythmia-free survival in MTWA negative patients was 79% compared to 64% at two years (p=0.0004); in nonischemic subgroups, 88% compared to 71% at two years (p=0.015). The 79% arrhythmia-free survival in MTWA negative patients with ischemic cardiomyopathy was much lower than reported in previously published studies (Bloomfield, 2006; Hohnloser, 2003; Bloomfield, 2004).

In contrast to the earlier studies, 16% of the patient population experienced syncope before inclusion, which represented a higher-risk population for ventricular tachyarrhythmia events (Cantillon, 2007). An additional limitation of this study was the assessment of MTWA using an invasive atrial pacing protocol, compared with earlier studies assessing MTWA noninvasively with a treadmill or exercise-induced protocol. Although their negative predictive value may be similar, one published study suggests that the predictive accuracy of an invasive, atrial pacing protocol may be inferior to noninvasive, exercise testing for risk stratification of patients with ischemic LV dysfunction (Rashba, 2002). Finally, the lack of a homogeneous patient population limits the comparison of MTWA and EPS, as EPS yields different predictive efficacy in ischemic and nonischemic heart disease. The predictive efficacy of MTWA testing in LV dysfunction in the Cantillon and other peer-reviewed published studies differs according to the underlying pathology of LV dysfunction and to the presence or absence of additional clinical risk features. Considering these factors, Klingenheben (2007) suggests that any recommendations on the use of MTWA should be based on interventional trials in well-defined patient populations.

In 2008, two prospective trials were published. The Microvolt T-Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients (MASTER) trial enrolled 575 patients from 50 U.S. centers who met MADIT-II criteria for a prophylactic ICD (Chow, 2008). All patients underwent MTWA followed by ICD implantation. The minimum follow-up was two years with annual MTWA. Results of MTWA were classified as either positive (51%), negative (37%) or indeterminate (12%). Indeterminate and positive results were grouped together as "non-negative." The primary endpoint was a ventricular tachyarrhythmic event (VTE), defined as either SCD or an appropriate ICD discharge. There were 70 VTEs during the follow-up period. A non-negative MTWA result was not associated with a VTE (hazard ratio=1.26). The authors concluded that the MASTER trial demonstrated that MTWA results do not identify MADIT II-indicated patients who are more or less likely to receive appropriate ICD therapy. The strengths of this trial include its large size, prospective design, uniform treatment with ICDs and standardization of ICD programming. Gold and colleagues (2008) reported on a prospective substudy of the randomized SCD-HeFT trial, which included 490 patients at 37 clinical sites. A total of 146 patients were randomized to amiodarone drug therapy, 178 to placebo therapy and 166 to ICD implantation. The primary endpoint was SCD, a sustained ventricular tachyarrhythmia or an appropriate ICD discharge. Patients were followed for a median of 30 months. MTWA results were classified as negative (22%), positive (37%) or indeterminate (41%). No significant difference in event rates was found between any MTWA category. The authors concluded that MTWA was not useful to predict arrhythmic events in patients participating in the SCD-HeFT trial. Specifically, MTWA results did not predict life-threatening ventricular arrhythmias or appropriate ICD shocks. The authors hypothesized that the more favorable results of MTWA in earlier uncontrolled trials were related to either 1) enrollment of low risk patients resulting in an increase in the negative predictive value; or 2) selection bias in single center studies; or 3) bias related to uncontrolled use of ICDs with different programming parameters.

While the initial trials of ICD as a primary prevention strategy (i.e. MADIT-1) included results of an electrophysiologic study (EPS) as a patient selection criteria, subsequent trials (i.e. MADIT-II) were specifically designed to eliminate EPS as a patient selection criteria, which were based on a history of myocardial infarction and an ejection fraction less than 30-35%. The MASTER trial and substudy of the SCH-HeFT trial, reviewed above, studied MWTA alone as a technique for further risks stratification. In contrast the ABCD (Alternans Before Cardioverter Defibrillator) trial compared EPS and MTWA as a risk stratification tool in a slightly different patient population, i.e. those ischemic heart disease and an ejection fraction of less than 40% and documented non-sustained ventricular tachycardia (Costantini, 2009). This trial was specifically designed to test the hypothesis that in patients with coronary artery disease and reduced ejection fraction, MTWA would perform at least as well as EPS to identify increased risk for sudden death. It should be noted that current candidacy for ICD, based in part on the results of the MADIT II trial, is not dependent on the results of EPS.

A total of 566 patients were enrolled and underwent testing with both MTWA and EPS. Patients with either a positive MTWA or EPS study underwent ICD implantation. Patients were followed for 1.9 years. The primary endpoint was appropriate ICD discharge or sudden cardiac death; 65 of the 566 met this endpoint. The main objective of the ABCD trial was to determine if risk stratification based on noninvasive MTWA was noninferior to invasive EPS study based on a comparison of the positive and negative predictive values. The non-inferiority margin was set at 10%. There was no significant difference in these values in predicting the primary endpoint. 

As noted in an accompanying editorial, results of noninferiority studies must be evaluated very carefully, particularly the noninferiority margins (Feld, 2009). For example, with the non-inferiority margin set at 10% and the positive predictive value reported as 11.1%, MTWA would only need to achieve a positive predictive value of 1.1% to be considered noninferior. Additionally, the PPV of both MTWA and EPS was low, suggesting that regardless of the method used, the number of ICDs inserted that actually benefit the patient will remain low.

Conclusions
It is well recognized that the left ventricular ejection fraction (LVEF) is a very imprecise criterion for ICD as a primary prevention technique for sudden cardiac death. Specifically, the vast majority of patients will not benefit, either because the ICD will never discharge, will discharge inappropriately, or will not prevent SCD. At the same time, these patients will be exposed to the morbidity associated with the ICD. Therefore, there has been keen interest in MTWA as a technique to refine patient selection criteria for an ICD, particularly because MTWA assesses the electrophysiologic substrate of the heart, which is more directly related to risk of arrhythmia than EF. Despite initial studies reporting that normal MTWA results were associated with a high negative predictive value for ventricular arrhythmias, larger prospective studies have reported disappointing results. The MASTER trial was the largest prospective, multicenter trial examining the role of MTWA in patients meeting criteria for the MADIT-II trial, and the SCD-HeFT substudy examined MTWA in a randomized group of patients. Both of these trials, which controlled ICD programming, reported that MTWA was not predictive for ventricular arrhythmias or appropriate ICD discharges.

At present, neither the American College of Cardiology nor CMS recommend withholding, based on MTWA results, an ICD from a patient meeting the criteria established in randomized clinical trials of ICD therapy (MADIT-II/SCD-HeFT) (Goldberger 2008, Zipes, 2006; CMS, 2008).

Epidemiology
Sudden cardiac death (SCD) is one of the most common causes of death after a myocardial infarction or in patients with dilated cardiomyopathy. There is intense interest in risk stratification to target therapy. In the United States, SCD results in approximately 400,000 deaths annually. Ventricular tachyarrhythmias, where the heart beats very fast due to abnormal ventricular contractions, are the most common cause of SCD. Examples of ventricular tachyarrhythmias include ventricular tachycardia (rapid ventricular contractions) and ventricular fibrillation (very rapid, weak, irregular and ineffective ventricular contractions). Patients most at risk for these heart rhythm disturbances include those with a recent myocardial infarction (heart attack), congestive heart failure, coronary artery disease, a family history of major ventricular arrhythmias, and/or dilated cardiomyopathy (disease of the heart muscle that causes the heart to get larger or dilate).

Functional Description
Microvolt T-wave alternans (MTWA) refers to a test measuring beat-to-beat electrocardiographic (EKG) variability in the amplitude of the T-wave, which was first recognized by Lewis in 1910. T-wave alterations are felt to represent abnormalities in intracellular calcium handling that may provoke re-entrant ventricular tachyarrhythmias (Armoundas, 2002). A routine EKG cannot detect these small fluctuations, and thus, this test requires specialized sensors to detect the fluctuations and computer algorithms to evaluate the results. MTWA is a provocative test that necessitates gradual elevation of the heart rate to above 110 beats per minute and can be performed in conjunction with an exercise tolerance stress test.

The magnitude of the MTWA is measured as microvolts. A value of 1.9 microvolts or greater above baseline is considered a positive test. MTWA is heart-rate dependent and is usually measured while the heart rate is elevated for several minutes by means of exercise, pacing or pharmacologic stress. The test can be performed by a supervised technician in approximately 30 minutes. Multiple electrode noise-reducing sensors are used to record the EKG signals. This spectral analytic method (Analytic Spectral Method™ using Micro-V™ Alternans Sensors, Cambridge Heart, Inc., Tewksbury, MA) uses specialized signal-processing algorithms to process the signals used to determine the amplitude of the alternans over background noise. For a positive result, the MTWA test must detect sustained alternans meeting amplitude criteria and be consistently present above an onset heart rate of 110 beats/minute or less. A negative test does not meet the alternans amplitude criterion; there must be at least one minute of data collected at a heart rate of 105 beats/minute or higher without significant alternans. Tests that do not qualify as positive or negative are classified as "indeterminate."

In May 2008, CMS reaffirmed their coverage of MTWA and found insufficient evidence to conclude that MTWA using other algorithm methods, such as the modified moving average (MMA) algorithm, would improve health outcomes for Medicare patients at risk for sudden cardiac death (CMS, 2008). There are several devices, along with this processing software, that have been FDA approved for performing MTWA, including the HeartWave Alternans Processing System^™, the Model APS Alternans Processing System^™, and the CH 2000 Cardiac Diagnostic System^™ (Cambridge Heart, Inc., Tewksbury, MA).

Other alternatives to MTWA testing for arrhythmia risk stratification that have been studied include electrophysiologic testing, ejection fraction testing, EKG testing, continuous Holter EKG monitoring, heart rate variability, signal-averaged EKG, and baroreceptor sensitivity testing.

Baroreceptor sensitivity testing: a test to evaluate patient propensity toward nervous system effects on the heart rate and rhythm when the patient becomes frightened, overly stressed, or overtired

Electrocardiography (EKG or ECG): the tracing of graphic records of the variations in electrical potential caused by electrical activity of the heart muscle and detected at the body surface, as a method for studying the action of the heart muscle

Electrophysiology studies (EPS): an invasive test where a catheter with an electrode is inserted into the ventricle chamber of the heart for analysis of the potential for arrhythmias, which are induced and then treated with intravenous medications

Holter monitoring: this noninvasive device allows for continuous ambulatory heart rhythm recording for a limited period of time, usually 24-48 hours, with subsequent physician interpretation of the recorded results

Left ventricular ejection fraction (LVEF): the percentage of the total blood volume in the left ventricle, which is ejected or pumped out into the bloodstream when the heart contracts during each heartbeat; this percentage is used as a measure of heart health and function

Tachycardia: a rapid heart rate, especially one above 100 beats per minute in an adult

T-wave alternans: the heartbeat-to-heartbeat variability in the shape of the T-wave on the EKG

Ventricular tachyarrhythmia: tachycardia that starts in one of the ventricles of the heart; a potentially unstable rhythm that may result in fainting, low blood pressure, shock, or sudden death

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Not Medically Necessary or Investigational and Not Medically Necessary:
For the procedure code listed below, when the code describes a procedure indicated in the Position Statement section as not medically necessary or investigational and not medically necessary.  

Peer Reviewed Publications:

1. Armoundas A, Tomaselli G, Esperer H. Pathophysiological basis and clinical application of T-wave alternans J Am Coll Cardiol. 2002; 40:207-217.
2. Baravelli M, Salerno-Uriarte D, Guzzetti D, et al. 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; 105(1):53-57.
3. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005; 352:225-237.
4. Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T-wave alternans tests. J Cardiovasc Electrophysiol. 2002; 13:502-512.
5. Bloomfield DM, Bigger JT, Steinman RC, et al. Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol. 2006; 47(2):456-463.
6. 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. Circ. 2004; 110:1885-1889.
7. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med. 2000; 342:1937-1945.
8. Cantillon DJ, Stein KM, Markowitz SM, et al. Predictive value of microvolt T-wave alternans in patients with left ventricular dysfunction. J Am Coll Cardiol. 2007; 50:166-173.
9. Chow T, Joshi D. Microvolt T-wave alternans testing for ventricular arrhythmia risk stratification. Expert Rev Cardiovasc Ther. 2008; 6(6):833-842.
10. Chow T, Kereiakes DJ, Bartone C, et al. Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2006; 47(9):1820-1827.
11. Chow T, Kereiakes DJ, Bartone C et al. Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy. J Am Coll Cardiol. 2007; 49(1):50-58.
12. Chow T, Kereiakes DJ, Onufer J, et al. MASTER Trial Investigators. Does microvolt T-wave alternans testing predict ventricular tachyarrhythmias in patients with ischemic cardiomyopathy and prophylactic defibrillators? The MASTER (Microvolt T-Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients) trial. J Am Coll Cardiol. 2008; 52:1607-1615.
13. Cleland JG, Coletta AP, Abdellah AT, et al. Clinical trials update from the American Heart Association 2007: CORONA, RethinQ, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy. Eur J Heart Fail. 2008; 10(1):102-108.
14. Costantini O, Hohnloser SH, Kirk MM, et al. ABCD Trial Investigators. The ABCD (Alternans Before Cardioverter Defibrillator) Trial: strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention. J Am Coll Cardiol. 2009; 53(6):471-479.
15. Costantini O, Kaufman ES, Bloomfield DM, et al. Patients with a nonischemic cardiomyopathy and a negative T-wave alternans stress test are at low risk of death. Circulation. 2004; 110(suppl III):667.
16. Feld GK, Clopton P.  Comparability of noninvasive microvolt T-wave alternans versus invasive ventricular programmed stimulation to guide implantable cardioverter-defibrillator implantation in patients at risk of sudden death. J Amer Coll Cardiol. 2009; 53:480-482.
17. Gehi AK, Stein RH, Metz LD, et al. Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events. J Am Coll Cardiol. 2005; 46(1):75-82.
18. Gold MR, Bloomfield DM, Anderson KP, et al. A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification. J Am Coll Cardiol. 2000; 36(7):2247-2253.
19. Gold MR, Ip JH, Costantini O, et al. Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: primary results from the T-wave alternans sudden cardiac death in heart failure trial substudy. Circulation. 2008; 118(20):2022-2028.  
20. Grimm W. Quantitative assessment on microvolt T-wave alternans (MTWA) in 204 consecutive patients with congestive heart failure. J Cardiovasc Electrophysiol. 2005; 16(11):1263-1264.
21. Hohnloser SH, Ikeda T, Bloomfield DM, et al. T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation. Lancet. 2003; 362:125-126.
22. Ikeda T, Saito H, Tanno K, et al. T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. Am J Cardiol. 2002; 89(1):79-82.
23. Ikeda T, Sakata T, Takami M, et al. Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction. A prospective study. J Am Coll Cardiol. 2000; 35(3):722-730.
24. Klingenheben T. Microvolt T-wave alternans for arrhythmia risk stratification in left ventricular dysfunction: which patients benefit? J Am Coll Cardiol. 2007; 50:174-175.
25. Klingenheben T, Zabel M, D'Agostino RB, et al. Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure. Lancet. 2000; 356(9230):651-652.
26. Mathew ST, Patel ND, Singh BK. T-wave alternans, a potential non-invasive marker for ventricular arrhythmias. Acta Cardiol. 2005; 60(6):639-649. 
27. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002; 346(12):877-883.
28. Myles RC, Jackson CE, Tsorlalis, et al. Is microvolt T-wave alternans the answer to risk stratification in heart failure? Circulation. 2007; 116(25):2984-2991.
29. Narayan SM. T-wave alternans and the susceptibility to ventricular arrhythmias. J Am Coll Cardiol. 2006; 47(2):269-281.
30. Rosenbaum DS. T-wave alternans in the sudden cardiac death in heart failure trial population: signal or noise? Circulation. 2008; 118(20):2015-2018.
31. Salerno-Uriarte JA, De Ferrari GM, Klersy C, et al. 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; 50(19):1896-1904.
32. Tapanainen JM, Still AM, Airaksinen KE, et al. Prognostic significance or risk stratifiers of mortality, including T-wave alternans, after acute myocardial infarction: Results of a prospective follow-up study. J Cardiovasc Electrophysiol. 2001; 12:645-652.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2004; 44:671-719.
2. Antman EM, Hand M, Armstrong PW, et al. JACC 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008; 51:210-247. 
3. Blue Cross Blue Shield Association. Microvolt T-wave alternans testing to risk stratify patients being considered for ICD therapy for primary prevention of sudden death. TEC Assessment, 2007; 21(14).
4. Centers for Medicare and Medicaid Services (CMS). Decision Memo: Microvolt T-wave Alternans. CAG-00293R. May 12, 2008. Available at: http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?from2=viewdecisionmemo.asp&id=213&. Accessed on January 5, 2009. 
5. Centers for Medicare and Medicaid Services (CMS). National Coverage Determination (NCD): Microvolt T-wave Alternans (MTWA). NCD #20.30. Effective: March 24, 2006. Available at: http://www.cms.hhs.gov/transmittals/downloads/R49NCD.pdf. Accessed on January 5, 2009.
6. Goldberger JJ, Cain ME, Hohnloser SH, et al. American Heart Association Council on Clinical Cardiology, American Heart Association Council on Epidemiology and Prevention; American College on Cardiology Foundation; Heart Rhythm Society. AHA/ACC Foundation/Heart Rhythm society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the AHA Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. Heart Rhythm. 2008; 5(10):e1-21.
7. Hayes, Inc. Hayes Medical Technology Directory. Microvolt T-Wave Alternans to Identify Risk of Ventricular Arrhythmias and Sudden Cardiac Death. Lansdale, PA: Hayes, Inc: July 31, 2002. Search updated May 22, 2008.
8. Kadish AH, Buxton AE, Kennedy HL, et al. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography: a report of the American College of Cardiology/American Heart Association/American College of Physicians-American Society of Internal Medicine Task Force on Clinical Competence (ACC/AHA Committee to develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography). Circ. 2001; 104:3169-3178.
9. Strickberger SA, Benson DW, Biaggioni I, et al. AHA/ACCF Scientific Statement on the Evaluation of Syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation in Collaboration with the Heart Rhythm Society. J Am Coll Cardiol. 2006; 47:473-484.
10. Zipes DP, Camm AJ, Borggrefe M, et al. American College of Cardiology/American Heart Association Task Force; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm    Association; Heart Rhythm Society. ACC/AHA/ESC 2006 Guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death - Executive Summary. A report of the ACA/AHA Task Force and the European Society of Cardiology Committee for Practice Guidelines. Circulation. 2006; 114(10):e385-484.

1. American Heart Association (AHA). Available at: http://www.americanheart.org/presenter.jhtml?identifier=1200000. Accessed on January 5, 2009.
2. American College of Cardiology (ACC). Available at: http://www.acc.org/. Accessed on January 5, 2009.

Microvolt T-Wave Alternans
MTWA
T-Wave Alternans

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