Description:
Microvolt T-wave alternans (MTWA) refers to a beat to beat variability in the amplitude of the T-wave. Because a routine electrocardiogram (EKG) cannot detect these small fluctuations, this test requires specialized sensors to detect the fluctuations and computer algorithms to evaluate the results. T-wave alternans is measured by a provocative test that requires gradual elevation of the heart rate to more than 110 beats per minute. The test can be performed in conjunction with an exercise tolerance stress test. Test results are reported as the number of standard deviations (SDs) by which the peak signal of the T-wave exceeds the background noise. This number is referred to as the alternans ratio. An alternans ratio of three or greater is typically a positive result, an absent alternans ratio is considered a negative result and other values are indeterminate.

The presence of T-wave alternans has been investigated as a risk factor for fatal arrhythmias and sudden cardiac death in patients with a history of myocardial infarction, congestive heart failure or cardiomyopathy. Patients with these disorders at high risk for sudden cardiac death may be treated with medications to suppress the emergence of arrhythmias or undergo implantation of cardiac defibrillators to terminate tachyarrhythmias when they occur. Since sudden cardiac death is one of the most common causes of death after an MI or in patients with dilated cardiomyopathy, there is substantial interest in risk stratification to target therapy.

Patient groups are categorized into those who have not experienced a life-threatening arrhythmia (i.e., primary prevention) and those who have (i.e., secondary prevention). Those who have already experienced an arrhythmia are already at high risk and probably do not require testing. T-wave alternans is one of many risk factors that have been investigated for identifying candidates for primary prevention. Others include left ventricular ejection fraction (LVEF), arrhythmias detected on Holter monitor or electrophysiologic studies, heart rate variability and baroreceptor sensitivity. Signal-average electrocardiography (SAECG) is another technique for risk stratification.

T-wave alternans has also been investigated as a diagnostic test for patients with syncope of unknown origin and as a noninvasive test to identify candidates for further invasive electrophysiology testing of the heart.

Related Policies
20204 Signal-Averaged Electrocardiography

Policy:
T-wave alternans is considered INVESTIGATIONAL as a technique of risk stratification for primary or secondary prevention* of fatal arrhythmias and sudden cardiac death in patients with a history of myocardial infarction, congestive heart failure, cardiomyopathy or other cardiac disorders such as long-QT syndrome (e.g., Brugada syndrome).

*Primary prevention refers to patients who have not experienced a life-threatening arrhythmia. Secondary prevention refers to patients who have experienced a life threatening arrhythmia.

Policy Guidelines
The following CPT code specifically identifies T-wave alternans:

93025: Microvolt T-wave alternans for assessment of ventricular arrhythmias

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational. However, this policy considers specific applications of an FDA-approved device as investigational. Alternatively, FDA-approved devices may be assessed on the basis of their medical necessity.

Rationale:
Prognostic or risk stratification test evaluation consists of:

1. Appraising test technical performance, including definitions of positive and negative results and reproducibility of the test.
2. Determining how accurately the test discriminates patients who will, from those who will not, experience the event of interest.
3. Evaluating the impact of test results on clinical management of the patient and a determination whether changes in clinical management result in an improvement of overall health outcomes.

Primary prevention implantable cardioverter-defibrillators (ICD) trials (e.g., MADIT-II and SCD-HeFT) have changed the perspective on selection and risk stratification for use of ICDs.¹ In the MADIT-II trial, implantable defibrillators were shown to be effective in patients selected on the basis of prior myocardial infarction (MI) and reduced ejection fraction. SCD-HeFT inclusion criteria required reduced ejection fraction but not previous MI. Prior studies of implantable defibrillators had selected patients using results of electrophysiologic testing and symptoms.^2,3 Given results from these trials, it is critical whether any additional risk stratification tool(s) can identify with sufficient accuracy patients who might or might not benefit from ICD implantation. For example, can T-wave alternans testing identify patients who would otherwise be appropriate for an ICD based in trial inclusion criteria, but who would actually not benefit from an ICD? (Note: Policy No. 70144 addresses the use of ICDs and patient selection criteria.)

The rationale for T-wave alternans testing is primarily that patients with a negative result will not benefit from an ICD. Accordingly, the most convincing evidence would be obtained from a randomized trial restricted to alternans-negative patients. Such a trial is lacking. Evidence from prospective cohort studies can accurately define the predictive ability of MTWA for sudden cardiac death. This evidence on risk may impact clinical management, if there are well-defined levels of risk that are linked to different management strategies.

Literature Review:
TEC Assessments. A June 2005 TEC Assessment evaluated the use of microvolt T-wave alternans (MTWA) to risk stratify patients in whom ICDs would be used for primary prevention of sudden cardiac death.⁴ The Assessment identified 18 studies using MTWA to prospectively stratify the risk of a subsequent event (total N = 2,931). Most studies interpreted MTWA blinded to other information. The incidence of endpoints (either ventricular tachyarrhythmic events [VTEs] or death) ranged from 3 percent to 51 percent across studies. Six studies included patients with ischemic cardiomyopathy, four nonischemic cardiomyopathy and eight patients selected by a variety of means, such as those referred for electrophysiologic testing.

Two patient indications were considered:

1. Patients eligible for ICD placement for primary prevention of sudden death
2. Patients not eligible for ICD placement

It is possible that the negative or positive predictive value (NPV, PPV) of MTWA results might be used to support decision-making regarding ICD placement. Specifically, for the first patient indication, negative MTWA results might be used to identify a subset of patients at low likelihood of subsequent VTEs and, thus, unlikely to benefit from ICD placement. While a few studies found that MTWA testing had high sensitivity and high NPV for future VTE, there was considerable variation in diagnostic performance in the published literature. Reported sensitivities ranged from 75 percent to 100 percent, negative predictive values from 73 percent to 100 percent and likelihood ratios for a negative test result varied between 0 and 0.42. The reasons for variation in diagnostic performance characteristics are not well-established (recently suggested related to varied use of beta blockers during testing⁵ as later discussed). Differences in pretest risk of VTE would most influence NPV. However, the Assessment also noted that it would also be important to understand whether MTWA diagnostic performance might vary according to population characteristics, such as etiology of cardiomyopathy. The diagnostic characteristics derived from the studies evaluated may not directly apply to patients eligible for ICD therapy.

The 2005 TEC Assessment concluded the evidence insufficient to determine whether the use of MTWA leads to improved net health outcomes or whether it is as beneficial as any established alternatives. Therefore, the use of MTWA testing for risk stratifying patients being considered for ICD therapy for primary prevention of sudden death did not meet the TEC criteria.

A 2006 TEC Assessment⁶ reviewed a smaller number of studies addressing the question of whether MTWA can identify patients who would otherwise meet clinical indications for ICDs but whose risk of death is so low that they would not benefit. The critical evidence sought was the absolute risk of VTE or sudden death in those patients who have a negative MTWA test, and whether it can be determined whether this risk is consistent with no potential benefit from ICD therapy. Three studies were reviewed restricting analyses to patients who met criteria for ICD therapy.

Bloomfield et al.⁷ followed 177 patients over an average of 20 months for all-cause mortality. Hohnloser et al.⁸ selected ICD-eligible patients from two previously published studies and followed them over two years for sudden cardiac death or cardiac arrest. Among those with a negative MTWA test, the actuarial two-year mortality rate was 3.8 percent. For those with a non-negative MTWA test, the actuarial two-year mortality rate was 17.8 percent. Arrhythmic outcomes were not reported in this study.

In Hohnloser et al.,⁸ patients who met MADIT-II criteria were pooled from two previously published studies. The study reported all-cause mortality, rates of sudden cardiac death or cardiac arrest and rates of VTE. For all-cause mortality estimated at two years, those with negative MTWA tests had a mortality rate of 12.5 percent, whereas those with non-negative MTWA tests had a mortality rate of 21.4 percent. For the primary outcome of sudden death or cardiac arrest, patients with negative MTWA tests had a 0 percent rate, and those with non-negative MTWA tests had a 15.6 percent rate. For the secondary outcome of all ventricular arrhythmic events, those with a negative MTWA test had a 5.7 percent rate, and those with non-negative tests had a 31.1 percent rate.

In Chow et al.⁹ a total of 768 consecutive patients with ischemic cardiomyopathy (left ventricular ejection fraction [LVEF] < 35 percent) and no prior history of ventricular arrhythmia were followed up for a mean of 18 months. Because event rates in the patients with and without ICDs are not comparable, only outcomes for the 376 patients who received only medical therapy were reported in the TEC Assessment. Thus, the results might be accompanied by potential selection bias. It appeared that the MTWA-negative patients who did not receive ICDs compared to the MTWA-negative patients who did receive ICDs had less severe heart failure (mean LVEF: 29.3 percent vs. 26.9 percent, respectively). At 18 months' mean follow-up, the all-cause mortality rate was 8.4 percent in MTWA-negative patients and 21.8 percent in MTWA non-negative patients. For arrhythmic deaths, the rate was 3.4 percent in MTWA-negative patients and 11.2 percent in MTWA non-negative patients.

The 2006 TEC Assessment concluded that although MTWA does stratify risk in ICD-eligible patients, evidence of sufficient accuracy to infer clinical utility was lacking. A modeling study by Chan et al.¹⁰ assumed a 2.7 percent annual sudden death rate among MTWA-negative patients and calculated that patients would still benefit from ICD therapy. Although modeling is not definitive, the study suggests that even the lower risk of arrhythmia in MTWA-negative patients is not low enough to preclude some benefit from ICD therapy.

Other Systematic Reviews. Results from two meta-analyses^5,11 suggest that some discrepancies in prior study results can be explained by lower predictive performance of MTWA in studies where beta-blockers were withheld prior to testing. The subgroup finding, although plausible, requires confirmation. Merchant et al.¹² conducted a patient-level analysis identifying studies enrolling more than 100 patients studied by the spectral method. Studies with 15 percent or more patients having ICDs were excluded, as were those in which 15 percent or more of the arrhythmic outcomes were attributed to appropriate ICD therapy. Studies (n = 2) using older protocol and instruments were also excluded. Of 17 identified studies, five met inclusion criteria. Patients with ICDs were excluded from the final analysis, yielding a sample of 2,883. Among patients with LVEF < 35 percent (n = 1,004) and negative MTWA testing, the annual sudden cardiac death rate was 0.9 percent versus 4.0 percent and 4.6 percent in the positive and indeterminate groups. The report did not state whether all selection criteria were established a priori. In addition, no sensitivity analyses were reported accounting for excluded patients and studies. Gupta et al.¹³ performed a study-level meta-analysis including 20 prospective cohort studies collectively enrolling 5,945 patients with MTWA obtained by the spectral method. They estimated that a negative MTWA decreased the annual fatal and non-fatal ventricular tachyarrhythmic event (VTE) rate from 5.9 percent to 2.6 percent in SCD-HeFT-like patients, and from 8.9 percent to 6.4 percent in MADIT-II-like patients. The authors concluded that spectral MTWA testing would not "sufficiently modify the risk of VTE to change clinical decisions."

Prospective Cohort Studies. Since the 2006 TEC Assessment, results from five multicenter studies provide the most informative evidence regarding the potential clinical utility of MTWA for risk stratification prior to ICD placement.

Between June 2001 and July 2004, the T-Wave Alternans in Patients With Heart Failure (ALPHA) registry enrolled 446 patients with New York Heart Association (NYHA) class II and III heart failure and LVEF equal to or less than 40 percent from nine centers across Italy.¹⁴ Heart failure etiologies included idiopathic dilated cardiomyopathy (n = 326), hypertensive cardiomyopathy (n = 72), valvular causes (n = 9) and others (n = 39). The primary endpoint was a composite of cardiac death and life-threatening ventricular arrhythmias. Mean patient age was 59 (SD = 12.5) years; 78 percent were male; and median follow-up was 19 months. MTWA results were negative in 34.6 percent, non-negative in 65.4 percent (44.8 percent positive, 20.6 percent indeterminate). The primary endpoint occurred in 29 (9.9 percent) of 292 with non-negative results, compared to four (2.6 percent) of 154 in the negative group. A survival model attempting to adjust for between-group differences in prognostic factors yielded a relative hazard of 4.0 (95 percent confidence interval [CI]: 1.2 to 13.3). The test's NPV through 18-months' follow-up was 97.3 percent (95 percent CI: 95.4 to 99.8 percent). Thirty-three patients with non-negative and six with negative results received ICDs. Sensitivity analyses accounting for the impact of ICD implantation on differential event occurrence yielded similar results — those with ICDs had more events recorded. These findings are consistent with most prior observational research finding negative MTWA results associated with fewer arrhythmic outcomes in nonischemic cardiomyopathy. Limitations of the study include lack of a randomized comparison or using MTWA results to direct ICD placement, and between-group differences in prognostic factors including age, LVEF, use of angiotensin-converting enzyme (ACE) inhibitors and digitalis and QRS duration. Although the investigators attempted to control for imbalances, the number of events (n=33) was insufficient to obtain valid estimates while accounting for more than a single prognostic factor or variable reflected in the wide confidence intervals. Furthermore, ICD placement is not indicated for primary prevention among individuals with LVEF greater than 35 percent. For these reasons, there is substantial uncertainty accompanying the results, and few conclusions can be drawn.

The Alternans Before Cardioverter Defibrillator (ABCD)¹⁵ cohort study enrolled primary prevention candidates for ICD implantation (sponsored by St. Jude Medical and Cambridge Heart). All patients underwent MTWA and an electrophysiological study (EPS). The primary goal was to demonstrate noninferiority of MTWA EPS testing in selecting primary prevention patients for ICD implantation — that the PPV and NPV of MTWA would be not worse than 10 percent of EPS PPV and NPV. A total of 629 participants were enrolled at 43 centers in the United States, Germany and Israel with ischemic cardiomyopathy, ejection fraction less than 40 percent and no history of cardiac arrhythmia (a primary prevention sample). Due to protocol violations, 63 participants were excluded, yielding an analytic sample of 566. Following EPS and MTWA testing, ICDs were implanted if results were positive for either test. When both tests were negative, ICD placement was left to the discretion of the treating physician — 70 percent of this group received ICDs. Patients were followed up a median of 1.9 years. The primary outcome was a composite of appropriate ICD therapy (n = 55) or arrhythmic death (n = 10). EPS testing was positive in 39 percent and negative in 61 percent. For MTWA results, an "MTWA strategy" was defined whereby patients with indeterminate tests were subsequently judged positive or negative based on the EPS result. These "strategies" had similar positive and negative predictive values for the composite outcome at one year — MTWA strategy: PPV 9 percent, NPV 95 percent; EPS: PPV 11 percent, NPV 96 percent. The results raise a number of issues. First, current evidence does not warrant ICD for primary prevention in patients with ejection fractions of 35 percent to 40 percent. Second, predictive values for MTWA reported were not independent of EPS results — those with indeterminate MTWA results were classified according to EPS results. Patients receiving ICDs for primary prevention would, however, not undergo EPS testing. Additionally, in the 30 percent of the MTWA-negative patients not receiving ICDs, the diagnosis of arrhythmic events was likely underestimated due to lack of electrogram recording. Finally, in some cases, approximately 50 percent of "appropriate" ICD shocks may be unnecessary, as many arrhythmias terminate spontaneously.¹⁶ While of interest, the study does not inform questions regarding the clinical utility of MTWA testing.

Microvolt T-Wave Alternans Testing for Risk Stratification of Post-MI Patients (MASTER I)¹⁷ was designed to determine whether MTWA predicted life-threatening ventricular tachyarrhythmic events (LTVTEs) in MADIT-II type patients (LVEF < 30 percent post-MI) treated with an ICD. Patients were enrolled at 50 centers across the United States (n = 575); mean age was 65 years (SD = 11), 84 percent were male and average follow-up was 2.1 (SD = 0.9) years. MTWA results were non-negative in 63 percent (51 percent positive and 12 percent indeterminate) — initially indeterminate tests were repeated. All patients received ICDs. In MTWA non-negative and negative patients, LTVTE occurred at annual rates of 6.3 percent and 5.0 percent, respectively. A non-negative MTWA result was not significantly associated with LTVTE. Although mean follow-up exceeded two years, there were few (n = 7, 1.2 percent) arrhythmic deaths. In contrast, the two-year sudden cardiac death rate in the MADIT-II ICD arm was 4.9 percent.¹⁸ Reasons for this difference are not clear but could reflect improved medical care, better defibrillator technology and programming or patient selection. Finally, some critique use of LTVTE as an endpoint, as not all will result in sudden cardiac death if left untreated. However, to alter these results would require differential rates of spontaneous termination in MTWA-negative and MTWA-positive patients — currently no evidence supports that suggestion.

The companion MASTER II results were presented at a late-breaking session of the 2008 American College of Cardiology (ACC) meeting and remain only in abstract form.¹⁹ The study enrolled 348 patients, mean age 64 years (SD = 10), 85 percent male, at 50 centers with ischemic-related LVEF of 31 – 40 percent. MTWA results were indeterminate in 45, positive in 132 and negative in 171; 48 percent of participants received ICDs. LTVTE occurred in seven MTWA-positive and four MTWA-negative patients. Event rates among patients with indeterminate tests were not reported. When patients with positive and negative MTWA results were compared, there was no association with LTVTE (hazard ratio: [HR]: 1.22, 95 percent CI: 0.34 to 4.39), although event rates were low. It is unclear why patients with indeterminate test results were excluded from the reported analyses.

A substudy of the SCD-HeFT trial evaluated the prognostic value of MTWA in 490 patients at 37 sites (of 2,521 patients enrolled in the trial).²⁰ The sample was similar to the larger SCD-HeFT population — 76 percent male, mean age 59 years (SD = 12), mean LVEF 24 percent (SD = 7), 49 percent had ischemic heart disease and 71 percent NYHA class II heart failure. MTWA results were positive in 37 percent, negative in 22 percent and indeterminate in 41 percent. Protocol recommended indeterminate tests to be repeated. Proportions MTWA-positive, MTWA-negative or MTWA-indeterminate results were similar in those randomly assigned to ICD/placebo and amiodarone. The primary composite endpoint included first appropriate ICD discharge, sustained ventricular tachycardia/fibrillation or sudden cardiac death. Patients randomly assigned to amiodarone were excluded from analysis of the primary endpoint due to inability to ascertain appropriate discharge. Over a median 30-month follow-up in the ICD/placebo arm, MTWA-positive patients (n = 139) did not have a distinguishable increase in events compared to MTWA-negative group (n = 72) (HR: 1.24, 95 percent CI: 0.60 to 2.59); nor MTWA-non-negative (n = 272) compared to MTWA-negative (n = 72) (HR: 1.28, 95 percent CI: 0.65 to 2.53). MTWA was not associated with all-cause mortality in the combined ICD/placebo and amiodarone sample. While commentators have pointed out the high proportion of indeterminate results, these results do not support clinical utility for MTWA prior to ICD placement in SCD-HeFT eligible patients.

Conclusions. Evidence from prospective cohort studies and systematic reviews establishes that MTWA can be used to risk stratify patients on the risk of sudden cardiac death. In patients who have indications for an ICD, a negative MTWA test lowers the risk of sudden cardiac death, while a positive test increases the risk. However, this risk stratification is unlikely to result in management changes that improve outcomes. The negative predictive value (NPV) of MTWA is not high enough to forego ICD placement in patients with a negative MTWA test. Other management changes, such as medication adjustments, may be made on the basis of this test, but the impact of these management changes is uncertain.

Practice Guidelines and Position Statements:
The 2006 American College of Cardiology(ACC)/American Heart Association(AHA)/European Society of Cardiology(ESC) 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death include T-wave alternans testing as IIa recommendation: "It is reasonable to use T-wave alternans for improving the diagnosis and risk stratification of patients with ventricular arrhythmias or who are at risk for developing life-threatening ventricular arrhythmias. (Level of Evidence: A)."²¹

A 2011 Consensus Guideline issued by the International Society for Holter and Noninvasive Electrocardiography concludes, "[o]verall, although TWA 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."²²

Clinical Input Received Through Physician Specialty Societies and Academic Medical Centers:
In response to requests, input was received from three academic medical centers while this policy was under review in 2008. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. The three reviewers disagreed with the proposed policy statement.

Summary:
Microvolt T-wave alternans is one available method to risk stratify patients who may be at risk for sudden cardiac death and has been proposed to assist in selecting patients for ICD treatment. Results from prospective multicenter studies enrolling various patient populations undergoing ICD placement as part of primary prevention strategies do not support clinical utility from MTWA used to risk stratify and therefore guide placement. This conclusion, expressed in the 2006 TEC Assessment, is also supported by recent prospective studies designed to evaluate the utility of MTWA and by pooled analyses. Therefore, this technology is considered investigational.

References:

1. 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):877-83.
2. Moss AJ, Hall WJ, Cannom DS et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335(26):1933-40.
3. Buxton AE, Lee KL, Fisher JD et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341(25):1882-90.
4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Microvolt T-Wave Alternans Testing to Risk Stratify Patients Being Considered for ICD Therapy for Primary Prevention of Sudden Death. TEC Assessments 2005; Volume 20, Tab 9.
5. Chan PS, Gold MR, Nallamothu BK. Do Beta-blockers impact microvolt T-wave alternans testing in patients at risk for ventricular arrhythmias? A meta-analysis. J Cardiovasc Electrophysiol 2010; 21(9):1009-14.
6. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Microvolt T-Wave Alternans Testing to Risk Stratify Patients Being Considered for ICD Therapy for Primary Prevention of Sudden Death. TEC Assessments 2006; Volume 21, Tab 14.
7. 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):1885-9.
8. 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):125-6.
9. 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):1820-7.
10. Chan PS, Stein K, Chow T et al. Cost-effectiveness of a microvolt T-wave alternans screening strategy for implantable cardioverter-defibrillator placement in the MADIT-II-eligible population. J Am Coll Cardiol 2006; 48(1):112-21.
11. Calo L, De Santo T, Nuccio F et al. Predictive value of microvolt T-wave alternans for cardiac death or ventricular tachyarrhythmic events in ischemic and nonischemic cardiomyopathy patients: a meta-analysis. Ann Noninvasive Electrocardiol 2011; 16(4):388-402.
12. Merchant FM, Ikeda T, Pedretti RF et al. Clinical utility of microvolt T-wave alternans testing in identifying patients at high or low risk of sudden cardiac death. Heart Rhythm 2012; 9(8):1256-64 e2.
13. 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):354-64.
14. 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):1896-904.
15. 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):471-9.
16. Ellenbogen KA, Levine JH, Berger RD et al. Are implantable cardioverter defibrillator shocks a surrogate for sudden cardiac death in patients with nonischemic cardiomyopathy? Circulation 2006; 113(6):776-82.
17. 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):1607-15.
18. Greenberg H, Case RB, Moss AJ et al. Analysis of mortality events in the Multicenter Automatic Defibrillator Implantation Trial (MADIT-II). J Am Coll Cardiol 2004; 43(8):1459-65.
19. Chow T, Kereiakes DJ, Onufer J et al. Prognostic value of microvolt T-wave alternans in patients with moderate ischemic left ventricular dysfunction: results from the MASTER II trial (abstract). J Am Coll Cardiol 2008; 51(10):A17.
20. 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):2022-8.
21. Zipes DP, Camm AJ, Borggrefe M et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114(10):e385-484.
22. 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):1309-24.
23. Decision Memo for Microvolt T-wave Alternans (CAG-00293N). 2008.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

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