Medical Policy



Subject: Microvolt T-Wave Alternans
Document #: MED.00041 Current Effective Date:    03/29/2017
Status: Reviewed Last Review Date:    02/02/2017

Description/Scope

This document addresses microvolt T-wave alternans testing, a noninvasive electrophysiologic study of the heart that measures beat-to-beat variability in the amplitude of the T-wave. Microvolt T-wave alternans testing has been proposed as a risk stratification tool to identify individuals 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 document for additional information:

Position Statement

Not Medically Necessary:

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

Investigational and Not Medically Necessary:

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

Rationale

ICDs have had a major impact on the treatment of ventricular tachyarrhythmias (VT). ICDs were initially used to treat individuals who had survived cardiac arrest or an episode of documented sustained VT. However, the majority of individuals who die from 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 select individuals. The Multicenter Unsustained Tachycardia Trial (MUSTT) demonstrated that, in individuals with a prior myocardial infarction (MI), 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) (Moss, 2002) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) (Bardy, 2005) were the two pivotal primary prevention trials that established the utility of ICD therapy for the primary prevention of SCD in individuals without a history of prior sustained VT. MADIT II addressed ICD use in individuals with prior MI and LVEF ≤ 0.30. SCD-HeFT addressed ICD therapy in individuals 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 individuals 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 individuals who meet the MADIT II or SCD-HeFT criteria. Studies of microvolt T-wave alternans (MTWA) have focused on the capability of this test to predict the risk of fatal arrhythmias and SCD in individuals with a history of MI, congestive heart failure (CHF), or cardiomyopathy. These high risk individuals 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.

In 2003, CMS conducted a subgroup analysis of MADIT II data that looked at the impact of QRS complex duration on individual health outcomes. Based on this analysis, CMS announced its intent to limit coverage of ICDs to individuals meeting the criteria for the MADIT-II trial with a QRS duration > 120 milliseconds, thereby reducing 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 individuals 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 individuals with LV dysfunction. Of the 549 available subjects in the study, 177 also met the MADIT II criteria (prior MI, LVEF ≤ 0.30). This subgroup formed the study group. The mean subject follow-up was 20 months; the primary outcome was all-cause mortality. The 2-year mortality rate in subjects 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 subjects with a QRS duration of > 120 milliseconds 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 at identifying a high-risk group and also better at identifying a low-risk group unlikely to benefit from ICD therapy. The authors also proposed that a normal MTWA test might be used to deselect individuals 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 candidate selection criteria for ICD implantation as a primary preventive therapy (Chow, 2006; Salerno-Uriate, 2007). The initial determination that an MTWA test was medically necessary for selection of a candidate for ICD placement was based in part on these trial results.

Several studies have challenged this role of MTWA. Cantillon and colleagues (2007) prospectively evaluated the effectiveness of MTWA in predicting arrhythmia-free survival and all-cause mortality in individuals with LV dysfunction. From a population of individuals referred for evaluation of syncope, nonsustained ventricular tachycardia (NSVT), or both, 286 subjects with an LVEF of ≤ 0.35 underwent EPS and MTWA assessment. Positive and indeterminate MTWA results were grouped as non-negative. Subjects 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 endpoint (hazard ratio [HR], 2.37; 95% confidence interval [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 subjects had improved 2-year arrhythmia-free survival compared with MTWA non-negative subjects (81% vs. 66%; p<0.0001). In subjects with ischemic heart disease, the arrhythmia-free survival in MTWA negative subjects was 79% compared to 64% at 2 years (p=0.0004); in nonischemic subgroups, 88% compared to 71% at 2 years (p=0.015). The 79% arrhythmia-free survival in MTWA negative subjects with ischemic cardiomyopathy was much lower than reported in previously published studies (Bloomfield, 2004; Bloomfield, 2006; Hohnloser, 2003).

In contrast to the earlier studies, 16% of the subjects experienced syncope before inclusion, which represented a higher-risk population for VT 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 individuals with ischemic LV dysfunction (Rashba, 2002). Finally, the lack of a homogeneous study 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 and a meta-analysis (van der Avoort, 2009) 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 study populations. The authors in the systematic review and meta-analysis (van der Avoort, 2009) suggest:

…there remains a need to examine MTWA in well-conducted randomized controlled trials as well as the ability of MTWA to predict long-term outcomes. While awaiting further quality studies, physicians and policy makers may wish to consider MTWA to help identify patients in the greatest need of aggressive primary prevention and ICD implantation.

Two prospective trials were published in 2008. The Microvolt T-Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients (MASTER) trial (Chow, 2008) enrolled 575 individuals from 50 United States centers who met MADIT-II criteria for a prophylactic ICD. All subjects underwent MTWA followed by ICD implantation. The minimum follow-up was 2 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 (HR, 1.26). The authors concluded that the MASTER trial demonstrated that MTWA results do not identify MADIT II-indicated individuals 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 individuals at 37 clinical sites. A total of 146 subjects were randomized to amiodarone drug therapy, 178 to placebo therapy and 166 to ICD implantation. The primary endpoint was SCD, a sustained VT or an appropriate ICD discharge. Subjects 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 subjects 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 individuals 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 (that is, MADIT-I) included results of an EPS as a participant selection criteria, subsequent trials (that is, MADIT-II) were specifically designed to eliminate EPS as a participant selection criteria, which were based on a history of MI and an EF < 30%-35%. The MASTER trial and substudy of the SCH-HeFT trial reviewed above studied MTWA alone as a technique for further risk stratification. In contrast, the ABCD (Alternans Before Cardioverter Defibrillator) cohort trial (Costantini, 2009) compared EPS and MTWA as a risk stratification tool in a slightly different study population, that is, subjects with ischemic heart disease and an EF of < 40% and documented NSVT. This trial was specifically designed to test the hypothesis that in individuals with coronary artery disease (CAD) and reduced EF, 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 individuals were enrolled and underwent testing with both MTWA and EPS. Subjects with either a positive MTWA or EPS study underwent ICD implantation. Subjects were followed for 1.9 years. The primary endpoint was appropriate ICD discharge or SCD; 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 non-inferior to invasive EPS study based on a comparison of the positive and negative predictive values. The noninferiority 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 non-inferiority studies must be evaluated very carefully, particularly the non-inferiority margins (Feld, 2009). For example, with the noninferiority margin set at 10% and the positive predictive value (PPV) reported as 11.1%, MTWA would only need to achieve a PPV of 1.1% to be considered non-inferior. 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 individual will remain low.

The Prospective Evaluation of Ventricular Tachyarrhythmic Events and Sudden Cardiac Death in Patients with Left Ventricular Dysfunction (PREVENT-SCD) trial (Shizuta, 2011) is a prospective multicenter study (n=453) evaluating the prognostic value of MTWA for VTs in individuals with cardiomyopathy and an LVEF of 40% or lower. A total of 280 eligible participants (62%) from 38 institutions in Japan underwent noninvasive MTWA testing using the spectral analytic method and were followed for an average of 36 months. The primary endpoint was a composite of SCD, sustained rapid VT or VF, and appropriate defibrillator therapy for rapid VT or VF. Study participants with indeterminate and MTWA positive tests were prospectively combined for analysis as 'non-negative' MTWA tests. The MTWA was reported as negative in 82 participants (29%), accounting for only 18% of the total study population. The 3-year event-free rate for the primary endpoint was significantly higher in MTWA-negative participants (97.0%) than in MTWA non-negative participants (89.5%, p=0.037) and those ineligible for the MTWA test (84.4%, p=0.003). Multivariable analysis identified both non-negative MTWA (HR, 4.43; 95% CI 1.02-19.2; p=0.047) and ineligibility for the MTWA test (HR, 6.89; 95% CI 1.59-29.9; p=0.010) to be independent predictors of the primary endpoint. The investigators concluded that MTWA showed a high negative predictive ability for lethal VT in individuals with LV dysfunction. Several important limitations were noted in this study. When taking into account those individuals ineligible for the MTWA test (n=173), the MTWA-negative participants accounted for only 18% of the study population; therefore, the high negative predictive value of MTWA for severe VT events (SVTE) was subject to selection bias, as this result was applicable to only a limited proportion of individuals with LV dysfunction. The investigators also noted the number of participants screened and excluded from the study was not recorded along with a relatively slow rate of participant enrollment, further accounting for some selection bias in the study population. In addition, the poor long-term prognosis of individuals ineligible for the MTWA study was reported as associated with the highest risk, not only for the primary endpoint of SVTE, but for all of the secondary endpoints, including VTE, all-cause death, and cardiac death. Other study limitations include an overestimate in arrhythmic events due to inclusion of appropriate ICD therapy in the composite primary endpoint analysis, and heterogeneity in other data collection and reporting due to the number of participating study sites without a core reporting laboratory. The investigators concluded that further study is warranted with a larger participant population and a longer follow-up period.

Gupta and colleagues (2012) performed a meta-analysis to determine the ability of spectrally-derived MTWA testing to modify the risk assessment of VTEs and SCD across a series of risk profiles using likelihood ratio (LR) testing, a measure of test performance independent of disease prevalence. The authors reviewed 20 prospective cohort studies consisting of 5945 subjects predominantly with prior MI or LV dysfunction. The analysis defined VTE as total and arrhythmic mortality and nonfatal sustained or ICD-treated VT. Summary estimates were created for positive and nonnegative MTWA results using a random-effects model, expressed as positive (LR+) and negative (LR-) LRs. Although there was a modest association between positive MTWA and VTE (relative risk [RR], 2.45, 1.58-3.79) and nonnegative MTWA and VTE (3.68, 2.23-6.07), test performance was poor (positive MTWA, LR+ 1.78, LR- 0.43; nonnegative MTWA, LR+ 1.38, LR- 0.56). Subgroup analyses of subjects classified as prior VTE, post-MI, SCD-HeFT type, and MADIT-II type had a similar poor test performance. A negative MTWA result would decrease the annualized risk of VTE from 8.85% to 6.37% in MADIT-II-type subjects and from 5.91% to 2.60% in SCD-HeFT-type subjects. Despite a modest association, the meta-analysis concluded that results of spectrally-derived MTWA testing do not sufficiently modify the risk of VTE to change clinical decisions.

Summary

It is well recognized that the LVEF is a very imprecise criterion for ICD as a prevention technique for SCD. Specifically, the vast majority of individuals will not benefit, either because the ICD will never discharge, will discharge inappropriately, or will not prevent SCD. At the same time, these individuals will be exposed to the morbidity associated with the ICD. Therefore, there has been keen interest in MTWA as a technique to refine the selection criteria for individuals who may be a candidate 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 individuals meeting criteria for the MADIT-II trial, and the SCD-HeFT substudy examined MTWA in a randomized group of study participants. 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 (ACC) nor CMS recommend withholding, based on MTWA results, an ICD from an individual meeting the criteria established in randomized clinical trials of ICD therapy (MADIT-II/SCD-HeFT) (CMS, 2015; Goldberger, 2008; Zipes, 2006). A consensus guideline prepared on behalf of the International Society for Holter and Noninvasive Electrocardiology and cosponsored by the Japanese Circulation Society, the Computers in Cardiology Working Group on e-Cardiology of the European Society of Cardiology, and the European Cardiac Arrhythmia Society states that although MTWA appears to be a useful marker of risk for arrhythmic and cardiovascular death, there is as yet no definitive evidence that it can guide therapy (Verrier, 2011).

Background/Overview

Epidemiology

SCD is one of the most common causes of death after an MI or in individuals with dilated cardiomyopathy. There is intense interest in risk stratification to target therapy. In the United States, SCD results in approximately 300,000 deaths annually. VTs, where the heart beats very fast due to abnormal ventricular contractions, are the most common cause of SCD. Examples of VTs include ventricular tachycardia (rapid ventricular contractions) and ventricular fibrillation (VF) (very rapid, weak, irregular and ineffective ventricular contractions). Individuals most at risk for these heart rhythm disturbances include those with a recent MI (heart attack), CHF, CAD, 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

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 VTs (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/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 1 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 beneficiaries at risk for SCD (CMS, 2008). On January 13, 2015, CMS determined that no National Coverage Determination (NCD) is appropriate at this time for MTWA testing using the MMA method for the evaluation of individuals at risk for SCD. Medicare coverage of MTWA using the MMA method will be determined by the local contractors. There are several devices and processing software that have received U.S. Food and Drug Administration (FDA) 510(k) clearance for the recording and measurement of MTWA, but no additional clearances have occurred since 2010.

Definitions

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: A noninvasive device allowing 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, used as a measure of heart health and function.

Tachycardia: A rapid heart rate, usually defined as a rate > 100 beats per minute in an adult.

T-wave alternans (TWA): The heartbeat-to-heartbeat variability in the shape of the T-wave on the EKG.

Ventricular tachyarrhythmia (VT): 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.

Coding

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, or when the code describes a procedure indicated in the Position Statement section as not medically necessary or investigational and not medically necessary.

CPT  
93025 Microvolt T-wave alternans for assessment of ventricular arrhythmias
   
ICD-10 Diagnosis  
  All diagnoses
   
References

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(3):225-237.
  4. 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.
  5. Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T-wave alternans tests. J Cardiovasc Electrophysiol. 2002; 13:502-512.
  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. Circulation. 2004; 110(14):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. N Engl J Med. 2000; 342(26):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(2):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. 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.
  11. 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.
  12. Chow T, Kereiakes DJ, Onufer J, et al. 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(20):1607-1615.
  13. Costantini O, Hohnloser SH, Kirk MM, et al. 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.
  14. 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.
  15. 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(6):480-482.
  16. Gehi AK, Stein RH, Metz LD, et al. Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events: a meta-analysis. J Am Coll Cardiol. 2005; 46(1):75-82.
  17. 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.
  18. 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.
  19. 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.
  20. Gupta A, Hoang DD, Karliner L, et al. Ability of microvolt T-wave alternans to modify risk assessment of ventricular tachyarrhythmic events: a meta-analysis. Am Heart J. 2012; 163(3):354-364.
  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(9378):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(2):174-175.
  25. 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.
  26. Rosenbaum DS. T-wave alternans in the sudden cardiac death in heart failure trial population: signal or noise? Circulation. 2008; 118(20):2015-2018.
  27. 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.
  28. Shizuta S, Ando K, Nobuyoshi M, et al. Prognostic utility of T-wave alternans in a real-world population of patients with left ventricular dysfunction: the PREVENT-SCD study. Clin Res Cardiol. 2012; 101(2):89-99.
  29. van der Avoort CJ, Filion KB, Dendukui N, Brophy JM. Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in patients with left-ventricular dysfunction: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2009; 9:5.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. 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).
  2. Centers for Medicare and Medicaid Services (CMS). National Coverage Anaylsis (NCR). Decision Memo: Microvolt T-wave Alternans. CAG-00293R. May 12, 2008. Available at: http://www.cms.gov/medicare-coverage-database/overview-and-quick-search.aspx. Accessed on December 7, 2016.
  3. Centers for Medicare and Medicaid Services (CMS). National Coverage Determination (NCD). Microvolt T-wave Alternans (MTWA). NCD #20.30. Revised: January 13, 2015. Available at: http://www.cms.gov/medicare-coverage-database/overview-and-quick-search.aspx. Accessed on December 7, 2016.
  4. 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 of 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-e21.
  5. Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009; 119(14):1977-2016.
  6. Verrier RL, Klingenheben T, Malik M, et al. Microvolt T-wave alternans physiological basis, methods of measurement, and clinical utility--consensus guideline by International Society for Holter and Noninvasive Electrocardiology. J Am Coll Cardiol. 2011; 58(13):1309-1324.
  7. 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-e484.
Websites for Additional Information
  1. American College of Cardiology - CardioSource (ACC). Available at: http://www.acc.org/. Accessed on December 7, 2016.
  2. American Heart Association (AHA). Available at: http://www.heart.org/HEARTORG/. Accessed on December 7, 2016.
Document History
Status Date Action
Reviewed 02/02/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Description, Background, References, and Websites for Additional Information sections.
Reviewed 02/04/2016 MPTAC review. Updated Rationale, References and Websites for Additional Information sections. Removed ICD-9 codes from Coding section.
Reviewed 02/05/2015 MPTAC review.
Format changes throughout document. Updated Background and References sections.
Reviewed 02/13/2014 MPTAC review. Updated Description, Background, and Reference sections.
Reviewed 02/14/2013 MPTAC review. Updated Rationale, Background, and References. Deleted Index section.
Reviewed 02/16/2012 MPTAC review. Updated Description, Rationale, Background, Definitions, References and Websites for Additional Information.
Reviewed 02/17/2011 MPTAC review. Updated Rationale, Background, Definitions, and References.
Reviewed 02/25/2010 MPTAC review. Updated Rationale, Background, and References.
Revised 02/26/2009 MPTAC review. Revised title to Microvolt T-Wave Alternans. Position Statements revised from medically necessary when criteria are met to not medically necessary and investigational and not medically necessary for all indications. Updated Description, Rationale, Discussion, Coding and References.
Reviewed 08/28/2008 MPTAC review. Clarified Description section and Position Statements. Updated Rationale, Definitions, and References.
  02/21/2008 The phrase "investigational/not medically necessary" was clarified to read "investigational and not medically necessary." This change was approved at the November 29, 2007 MPTAC meeting.
Reviewed 08/23/2007 MPTAC review. Updated Rationale and References.
Revised 09/14/2006 MPTAC review. Position Statement revised from investigational/not medically necessary for all indications to medically necessary when criteria are met.  Updated Rationale, Background, Coding, and References.
Reviewed 06/08/2006 MPTAC review. References and Rationale updated  
Reviewed 03/23/2006 MPTAC review. References updated.
Revised 04/28/2005 MPTAC review. Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.
Pre-Merger Organizations Last Review Date Document Number Title
Anthem, Inc.

04/27/2004

MED.00041

T-wave Alternans
WellPoint Health Networks, Inc.

09/23/2004

2.04.23

T-Wave Alternans