Archived Policies - Medicine
Risk Stratification Tests for Determining Arrhythmias (Signal-Averaged Electrocardiography [SAECG] and Microvolt T-Wave Alternans [MTWA])
Microvolt T-Wave Alternans (MTWA) as a technique of risk stratification for primary or secondary prevention of fatal arrhythmias and sudden cardiac death (SCD) may be considered medically necessary in patients who are at risk for developing life-threatening ventricular arrhythmias (e.g. known cardiac dysrhythmias, history of myocardial infarction, congestive heart failure, or cardiomyopathy).
Signal-Averaged Electrocardiography (SAECG), as a technique of risk stratification for arrhythmias after prior myocardial infarction (MI), is considered not medically necessary.
Other applications of SAECG are considered experimental, investigational and/or unproven, including but not limited to the following:
• Use in patients with cardiomyopathy,
• Use in patients with syncope,
• Assessment of success after surgery for arrhythmia,
• Detection of acute rejection of heart transplants,
• Assessment of efficacy of antiarrhythmic drug therapy, or
• Assessment of success of pharmacological, mechanical, or surgical interventions to restore coronary artery blood flow.
Patients considered at high risk of ventricular arrhythmias and thus sudden cardiac death (SCD) may be treated with drugs to suppress the emergence of arrhythmias, or may undergo implantation of an automatic implantable cardiac defibrillator (AICD), which promptly detects and terminates tachyarrhythmias when they occur. Since SCD, whether from arrhythmias or pump failure, is one of the most common causes of death after a previous MI, there is intense interest in risk stratification to target therapy.
SAECG and MTWA have been investigated as techniques of risk stratification for arrhythmic events in patients with a variety of cardiac conditions, including cardiomyopathy and prior history of myocardial infarction (MI). MTWA measures beat-to-beat variability, while SAECG measures beat-averaged conduction. Other risk factors include left ventricular ejection fraction, arrhythmias detected on Holter monitor or electrophysiologic studies, heart rate variability, and baroreceptor sensitivity.
Patient groups are divided 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.
SAECG is a technique involving computerized analysis of small segments of a standard EKG to detect abnormalities, termed "ventricular late potentials" (VLP), that would be otherwise obscured by “background” skeletal muscle activity. VLP reflect aberrant, asynchronous electrical impulses arising from viable isolated cardiac muscle bordering an infarcted area and are thought to be responsible for ventricular tachyarrhythmias.
MTWA refers to a beat-to-beat variability in the amplitude of the T-wave. A routine electrocardiogram (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 requires gradual elevation of the heart rate to above 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 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 considered a positive result, an absent alternans ratio is considered a negative result, and anything in between is considered indeterminate. MTWA 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.
For a diagnostic technology, evaluation consists of:
• Evaluation of the technical performance of the test, including definitions of positive and negative results and reproducibility of the test;
• Determination of sensitivity, specificity, and positive and negative predictive values for the different clinical situations under consideration, compared to a gold standard or reference standard; and
• Evaluation of the impact of the test result on the clinical management of the patient and a determination of whether the changes in clinical management result in an improvement of overall health outcomes.
Primary prevention ICD trials (e.g., MADIT-II and SCD-HeFT) have changed the perspective on selection and risk stratification for use of implantable defibrillators. In the MADIT-II trial, implantable defibrillators were shown to be effective in patients selected on the basis of prior MI and reduced ejection fraction (EF); SCD-HeFT also used reduced EF but did not require prior MI. Prior studies of implantable defibrillators had selected patients using results of electrophysiologic testing and symptoms. Given these specific clinical trials, it becomes critical whether any additional risk stratification test is a useful or efficient maneuver in improving identification of patients who benefit or do not benefit from therapy. For example, can MTWA testing identify patients who would otherwise qualify for an implantable defibrillator but who would actually not benefit from the procedure? Or alternatively, can microvolt T-Wave alternans (MTWA) testing identify patients who do not qualify for an implantable defibrillator under the selection criteria of these clinical trials but would nonetheless benefit?
An October 2005 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment evaluated the use of MTWA to risk stratify patients being considered for ICD therapy for primary prevention. The TEC 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 prevalence of endpoint events (either VTE or death) ranged from 3% to 51% across studies. Six studies included subjects with ischemic cardiomyopathy, four included nonischemic cardiomyopathy, and eight included subjects 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, and 2) patients who are not eligible for ICD placement. It is possible that the negative or positive predictive value of MTWA results might be used to support decision making regarding ICD placement. Specifically, in the first patient indication, negative MTWA results might be used to identify a subset of patients at low likelihood of subsequent ventricular tachyarrhythmic events (VTE) and thus unlikely to benefit from ICD placement. While a few studies did find that MTWA testing had high sensitivity and high negative predictive value for risk of future VTE, there was considerable variation in diagnostic performance in the published literature. Reported sensitivity ranged from 75% to 100%, negative predictive value from 73% to 100%, and likelihood ratios for a negative test result varied between zero and 0.42. The reasons for variation in diagnostic performance characteristics are not well-established. Differences in pretest risk of VTE would most influence negative predictive value; however, it would also be important to understand whether MTWA diagnostic performance might vary according to characteristics of the population such as etiology of cardiomyopathy.
For patients who would not otherwise be eligible for ICD placement, the TEC Assessment noted MTWA would be used for its positive predictive value to select patients who might be at increased risk of VTE and possibly benefit from an ICD. The most important clinical endpoint in determining the clinical effectiveness of ICD therapy is all-cause mortality rather than VTE alone. Certainly, ICD’s are effective by reducing mortality due to VTE. However, it is the balance of VTE-related sudden cardiac death and other causes of mortality that determines the effectiveness of ICD therapy, and this balance varies by population. In nine studies that reported positive predictive value (PPV) for MTWA in the TEC Assessment, positive predictive value ranged from 7% to 67%, and the likelihood ratios for a positive result generally ranged from 1.4 to 3.6 with one exception at 6.3. Positive predictive values vary widely, somewhat influenced by differences in population baseline risk, but the relatively low positive likelihood ratios also suggest that MTWA is not a very strong predictor of VTE. However, even if reliable prediction of VTE were possible with MTWA, this would still not address the question of effect of subsequent ICD therapy on total mortality, considering the balance of sudden cardiac death with other causes of mortality.
In their Practice Guidelines, the American College of Cardiology recommends that 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.
Signal-Averaged Electrocardiography (SAECG)
SAECG has been thoroughly studied as a risk stratification tool for potentially fatal arrhythmias in patients with a previous MI. As reviewed by the Agency for Health Care Policy and Research (AHCPR) in 1998, SAECG is associated with a low positive predictive value ranging from 8%–44%, depending on the population studied. In contrast, the negative predictive value (i.e., the ability to identify those patients who will not experience ventricular arrhythmias) ranges from 88%–97%, suggesting that the negative predictive value may be used to identify patients who would not benefit from antiarrhythmic therapy. However, a key statistic underlying the negative predictive value is the underlying prevalence of the outcome. Although sudden cardiac death is the most common cause of death in the one-year period after infarction, it is relatively uncommon (2.5%–11.3%) and declining, due to increasing use of thrombolytic therapy, aspirin, and beta-blockers. Thus, given the relative low incidence of arrhythmias, the high negative predictive value is not surprising.
In 1996, the American College of Cardiology published an expert consensus document that concluded that SAECG had an established or valuable role in clinical care in the following situations:
• Stratification of risk of developing sustained ventricular arrhythmias in patients recovering from MI who are in sinus rhythm without electrocardiographic evidence of bundle branch block or intraventricular conduction delay,
• Identification of patients with ischemic heart disease and unexplained syncope who are likely to have inducible sustained ventricular tachycardia,
• Stratification of risk of developing sustained ventricular arrhythmia in patients with nonischemic cardiomyopathy, or
• Assessment of success of operation for sustained ventricular tachycardia.
However, the ultimate validation of any diagnostic test is to determine how it is used in the management of patients, and whether the management decisions result in improved health outcomes. The following discussion focuses on the clinical use of SAECG as reported in clinical trials of antiarrhythmic therapies.
Over the past two decades, a large number of randomized clinical trials have evaluated the effectiveness of either antiarrhythmic drugs or AICD implantation in post-MI patients. These trials have generally used a variety of risk stratification criteria to positively select patients for intervention. By selecting patients with a sufficiently high risk of arrhythmia, the benefits of treating arrhythmia will hopefully outweigh any adverse effects of the treatment. For the purposes of this discussion, the most relevant studies are those that look at patients who have not experienced a prior episode of near fatal ventricular arrhythmia or aborted sudden death. Patients with a prior history of a potentially fatal arrhythmia are already at sufficiently high risk and are considered candidates for either antiarrhythmic therapy or AICD.
Initially it was thought that pharmacological suppression of premature ventricular contractions (PVCs), identified on post-MI monitoring, would reduce the incidence of subsequent sustained, symptomatic arrhythmias. The Cardiac Arrhythmia Suppression Trial (CAST) was a placebo-controlled, randomized trial that tested the efficacy of encainide, flecainide, or moricizine in reducing arrhythmic death in patients with a lowered ejection fraction and six or more PVCs per hour. CAST was terminated prematurely when an interim analysis suggested that the drug therapy was associated with an increase in the incidence in arrhythmic death. This trial raised concerns about proarrhythmic effects of antiarrhythmic drugs and has led to caution in the use of any antiarrhythmic drug therapy.
The drugs in the CAST trial are known as Class I antiarrhythmic, defined as those agents that slow conduction. After the failure of the CAST trial, research was focused on class III agents, which prolong repolarization. The most commonly researched member of this class of drugs is amiodarone. There have been a number of small randomized studies of amiodarone, but the largest are the EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial), both of which assessed the effect of amiodarone on mortality in patients with high-risk markers after MI. In the EMIAT trial, patients with a history of MI were stratified according to their ejection fraction. In the CAMIAT trial, patients were recruited based on results of Holter monitoring. Therefore, neither of these key trials used SAECG as a patient selection criterion.
The results of both of these trials suggested that while amiodarone was associated with a decreased risk of arrhythmias, there was no overall reduction in all-cause mortality. Therefore, the major finding of these trials focused on the safety of amiodarone, in contrast to the class I agents studied in the CAST trial. The clinical effectiveness of amiodarone is less certain and may be associated with a reduction of morbidity and quality of life associated with symptomatic arrhythmias, although this outcome has not been specifically studied. It is possible that a normal SAECG could be considered to deselect patients who would be unlikely to benefit from amiodarone therapy. However, this outcome has not been specifically studied, particularly since the overall benefit of amiodarone therapy is still controversial.
With the somewhat disappointing results of these drug trials, attention has turned toward the use of AICDs, particularly as these devices have become more sophisticated. Early generations of AICDs required thoracotomy for insertion but miniaturization has permitted outpatient insertion with the use of local anesthesia. With this reduction in the risk associated with AICDs, there was an interest in exploring their use in patients without a prior history of sustained, symptomatic ventricular arrhythmias. Several randomized studies have now been completed. The MADIT trial recruited post-MI patients with LVEF of less than 35%; non-sustained ventricular tachycardia identified on Holter monitoring or stress test, and inducible, procainide-resistant, sustained ventricular arrhythmia on electrophysiologic study (EPS). These characteristics were thought to identify a very high risk group for ventricular arrhythmias, in part due to the desire to have very high event rates to increase the power of the trial. The MADIT trial reported a marked reduction in mortality in those receiving a defibrillator compared to patients treated conventionally, mostly with amiodarone. Following the publication of the results, the U.S. Food and Drug Administration (FDA) approved expanded labeling for defibrillators in patients who met the MADIT criteria, Medicare announced coverage for AICD in this patient population, and the American College of Cardiology (ACC) has published guidelines endorsing the study results. As noted above, SAECG was not used as a patient selection criterion, and thus is not included as a recommended test as part of the ACC guidelines.
In contrast to the other trials reviewed above, the CABG-Patch trial used SAECG as a positive patient selection criterion. The CABG-Patch trial recruited patients scheduled for a CABG who had an EF of less than 36% and abnormalities on the SAECG. The use of an SAECG was based on a pilot study that showed an abnormal SAECG was associated with a mortality rate that was double that seen in those with a normal SAECG in the two years after CABG. Patients were randomized to a defibrillator group or a control group, and all received CABG. After an average follow-up of 32 months, there was no evidence of improved survival among those in the defibrillator group. However, it cannot be determined whether the failure of this trial was due to the selection criteria or the treatments being compared.
Therefore, based on the above review, it can be seen that the SAECG has not been successfully used as a patient selection criterion in the critical randomized trials investigating both drug and device antiarrhythmic therapy in the post-MI patient. In the majority of trials, it has not been included as a patient selection criterion, and the one trial in which it was used reported negative results.
A search of the literature based on the MEDLINE database was performed for the period of 1999 through January 2005. More recent trials investigating the use of AICD in post-MI patients have not provided clarity regarding the issue of risk stratification. The MADIT-II trial selected patients solely on the basis of LVEF, and showed a survival benefit among those randomized to AICD. Grimm and colleagues reported on the results of the Marburg Cardiomyopathy study, a prospective observational study designed to determine the clinical value of potential noninvasive arrhythmia risk predictors among 343 patients with idiopathic dilated cardiomyopathy and followed for 52 +/- 21 months for major arrhythmic events. Reduced LVEF and lack of beta blocker use were important risk factors, but results of SAECG and MTWA were not. Results of SAECG were found to only be a weak predictor of sudden cardiac death in a consecutive series of 700 patients with a history of acute myocardial infarction. No additional data have directly linked risk stratification information provided by SAECG to improved patient outcomes, improved efficiency, or reduced costs.
There are inadequate data to evaluate the impact on patient management of other applications of SAECG including, but not limited to: its use in patients with cardiomyopathy; assessment of success after surgery for arrhythmia; detection of acute rejection of heart transplants; assessment of efficacy of antiarrhythmic drug therapy; or assessment of success of pharmacological, mechanical, or surgical interventions to restore coronary artery blood flow. The (ACC) consensus document concluded that SAECG had an established role in identifying patients with syncope who may have inducible VT; however the data reported only modest sensitivity (73%) and poor positive predictive values. Thus, if used as a screening test to determine who should have electrophysiologic studies, the test will fail to detect many patients who have positive electrophysiologic studies.
A search of peer reviewed literature through July 2014 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.
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3. Julian, D.G., Camm, A.J., et al. Randomized trial of effect of amiodarone on mortality in patients with left ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators. Lancet (1997) 439(9053):667-74.
4. Cairns, J.A., Connolly S.J. et al. Randomized trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarization: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet (1997) 349(9053):675-82.
5. Bigger, J.T. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. New England Journal of Medicine (1997) 337(22):1569-75.
6. U.S. Department of Health and Human Services. Health Technology Assessment. Number 11. Signal-averaged electrocardiography (1998) Publication No. PB98-137227.
7. Gregoratos, G., Cheitlin, M.D., et al. ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation). Journal of the American College of Cardiology (1998) 31(5):1175-209.
8. Hohnloser, S.H., Klingenheben, T., et al. Identification of patients after myocardial infarction at risk of life-threatening arrhythmias. European Heart Journal (1999) 1(suppl C):C11-20.
9. Toubol, P. A decade of clinical trials; CAST to AVID. European Heart Journal (1999)1(suppl C):C2-10.
10. Buxton, A.E., Lee, K.L., et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. New England Journal of Medicine (1999) 341(25):1882-90.
11. Moss, A.J., Zareba, W., et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. New England Journal of Medicine (2002) 346(12):877-83.
12. Grimm, W., Christ, M., et al. Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Circulation (2003) 108(23):2883-91.
13. Huikuri, H.V., Tapanainen, J.M., et al. Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era. Journal of the American College of Cardiology (2003) 42(4):652-8.
14. Gehi, A.K., Stein R.H., et al. Microvolt T-Wave alternans for the risk stratification of ventricular tachyarrhythmia events: a meta-analysis. Journal of the American College of Cardiology (2005 July) 46(1):75-82.
15. Microvolt T-Wave Alternans Testing to Risk stratify Patients Being Considered for ICD Therapy for Primary Prevention of Sudden Death. Chicago, Illinois: Blue Cross Blue shield Association – Technology Evaluation Center Assessment Program (2005 October) 20(9):1-29.
16. Decision Memo for Microvolt T-Wave Alternans (CAG-00293N). U.S. Department of Health & Human Services. CMS—Centers for Medicare and Medicaid Services (2006 Mar 21) <http://www.cms.hhs.gov>.
17. Bloomfield, D.M., Bigger, J.T., et al. Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. Journal of the American College of Cardiology (2006) 47(2):456-63.
18. AAC/AHA/ESC Practice Guidelines Executive Summary. Journal of the American College of Cardiology (2006 September 5) 48(5):1064-1108.
19. Quarta, Giovanni, Marino, L, et al. The Microvolt T-Wave Alternans Test: An Emerging Tool for Risk Stratification of Sudden Cardiac Death. High Blood Pressure & Cardiovascular Prevention, Volume 14, Number 4 (2007) pp. 213-19.
20. Signal-Averaged Electrocardiography-Archived. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (December 2012) Medicine 2.02.04.
21. T-Wave Alternans-Archived. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (May 2013) Medicine 2.02.13.
|8/1/2015||Reviewed. No changes.|
|11/15/2014||Document updated with literature review. Coverage unchanged. CPT/HCPCS code(s) updated|
|10/15/2013||Literature reviewed. No changes.|
|2/15/2009||Revised/updated entire document, this policy is no longer scheduled for routine literature review and update.|
|11/1/2006||Revised/updated entire document|
|8/15/2003||Revised/updated entire document|
|3/1/2002||Revised/updated entire document|
|4/1/1999||Revised/updated entire document|
|9/1/1998||Revised/updated entire document|
|Title:||Effective Date:||End Date:|
|Risk Stratification Tests for Determining Arrhythmias (Signal-Averaged Electrocardiography [SAECG] and Microvolt T-Wave Alternans [MTWA])||10-15-2017||10-31-2018|
|Risk Stratification Tests for Determining Arrhythmias (Signal-Averaged Electrocardiography [SAECG] and Microvolt T-Wave Alternans [MTWA])||10-01-2016||10-14-2017|
|Risk Stratification Tests for Determining Arrhythmias (Signal-Averaged Electrocardiography [SAECG] and T-Wave Alternans)||08-15-2003||10-31-2006|