Microvolt T-wave Alternans

Generally, CMS is to be commended for its proposal to provide national coverage for reimbursement of Microvolt T-wave Alternans (MTWA). However, restricting coverage of MTWA testing to the spectral analytic method (thus limiting coverage to a single company’s product) is short-sited and does not allow coverage of other MTW systems that the FDA may approve for clinical use in the future.

As you are aware, MTWA is simply a natural phenomenon of the heart that can be used by the physician along with other information to risk stratify patients who may be at increased risk for sudden cardiac death. The method used to assess this natural phenomenon should provide an analytical result that is equivalent to that provided by other FDA-approved instruments that measure MTWA. For example, the Modified Moving Average Method has been previously cleared for sale by the FDA following an extensive demonstration that it provides results that are equivalent to the spectral analytical method. It seems clear that other methods of measuring MTWA are in development and may become available over the next few years. The FDA’s role is to determine if new methods are substantially equivalent to existing predicate devices. Thus, if the FDA approves a new device measuring MTWA as substantially equivalent to existing methodologies, then that device should be covered under the CMS policy. Limiting coverage to the spectral analytic method would not allow patients and their physicians to utilize potentially more cost effective tests that are cleared by the FDA and available to physicians. By definition, if the two methods are technically equivalent, then the clinical results derived from either one should apply to both.

In a sense, the issue is no different than a situation where a measurement is made by a ruler or a yardstick: so long each arrives at the same result, then it should not matter which measuring tool is used. To use another clinical example, if Medicare chooses to cover a diagnostic test, such as cholesterol, then it should not matter which methodology is used to perform the measurement, so long as each method gives an accurate result. We believe the same standard should be applied to MTWA. As a result, CMS should cover MTQA if it is performed by any methodology equivalent to existing methodologies. Thank you for the opportunity to comment.

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I am the editor of the European Web page on MicroVolt T Wave Alternans www.alternans.org

I am also author and co-author of several clinical papers on MTWA on PACE (1), Annals of Noninvasive Electrocardiology (2), Italian Heart Journal (3)and Italian Electrophysiology Journal (4).

This webpage is the reference for European cardiologists using MTWA alternans systems ( visited by 11.350 visitors in the last 5 years).

I am receiving several comments and requests of help from TWA users.

One of the most interesting question that I have received recently is "How I can interpretate the Time Domain MMA TWA Report ?".

I am not really able to answer to this question because there is no published criteria of interpretation of MMA Report. I am wandering how can a cardiologist make clinical use of the MMA TWA method if no interpretation criteria has been published. Should they use 25 or 100 microVolt limit as from Narayan paper (JACC, vol 47,No.2,2006)? What is the relation with 1,9 microVolt limit that is the standard of the Spectral Method? How can MMA method avoid Respiratory false alternans that is the first cause of false alternans?

I have reviewed and maintain in alternans.org extensive bibliography on Microvolt T-Wave Alternans. The literature has many prospective clinical studies all using Analytic Spectral Method as a standard with very clear interpretation standards. Clinical results are well documented as shown in your proposed decision. Interestingly in the most recent paper of Verrier and Nearing (Circulation. 2004;109:1864- 1869),where the MMA method is used, the Cambridge Heart CH2000 and High resolution electrodes are used for noise reduction and exported to the GE system (see Protocol in the same paper). I am unaware of any prospectively enrolled clinical studies utilizing MMA.

Despite I am not directly involved in CMS reimbursement, I would like to provide my experience to the matter. It makes sense for me to make test available as per your 21/12 publication for analytic spectral method.

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I write in strong support of the CMS proposed decision to provide national coverage for the use of microvolt T-wave alternans (MTWA) testing to evaluate patients at risk of sudden cardiac death. As detailed in the CMS review, this technology has been demonstrated to be an effective means of identifying patients at lost and high risk of sustained ventricular tachyarrhythmia. This decision will have a significant impact on improving the quality of the care of Medicare beneficiaries.

I would like to submit as part of the public comment period three recently published articles that present data that further support the proposed decision memorandum. These articles, in particular, confirm the excellent negative predictive value of the MTWA test.

A meta-analysis of prospective clinical trials (1) comprising 1,811, patients with left ventricular dysfunction and no known history of sustained ventricular tachyarrhythmia showed that patients who tested negative for MTWA and did not receive and ICD had a 2.0% annual mortality rate compared with a 7.4% annual mortality rate in comparable patients who did not undergo MTWA testing but did receive an ICD.

In addition, a major National Institute of Health (NIH) funded multi-center study has just appeared in the Journal of the American College of Cardiology (2). This study, conducted in patients with left ventricular dysfunction either on the basis of coronary artery disease or on the basis of non-ischemic dilated cardiomyopathy, confirms an extremely low event rate among patients who tested negative for MTWA and an elevated rate in the remaining patients. For the combined endpoint of all cause mortality plus sustained ventricular tachyarrhythmia the annual event rate among patients who tested negative for MTWA was 1.3% and among the remaining patients it was 8.1% (these annual event rates were computed from the reported multi-year data using the method described in Armoundas et al, 2005 (1) cited above).

A third study (3), conducted in 73 ischemic and non- ischemic patients with New York Heart Association class II heart failure, demonstrated no tachyarrhythmic events among patient who tested MTWA negative compared with a 42% event rate among MTWA positive patients at 27 months of follow-up.

The proposed decision correctly notes that the prospective clinical studies which establish the clinical utility of MTWA testing should be considered reasonable and necessary only when this method is used.

Several public comments on the proposed decision suggest eliminating this restriction. I disagree with this suggestion because comparable prospective clinical trial data do not exist for any means of measuring MTQWA other than the analytic spectral method. The accuracy and reliability of measuring MTQA depends exquisitely on the details of the implementation. The Cambridge Heart, Inc. system which implements the analytic spectral method involves advanced technology for signal acquisition (i.e. involving the use of multi-electrode noise-reducing sensors) and signal processing and established standards for clinical interpretation. An automated system to interpret the output of the test assures uniform clinical results.

MTQA testing is used to identify patients at high and low risk of sudden cardiac death. In order to ensure patient safety, one needs to validate the measurement technology with a large database of prospective clinical data that reliably demonstrates a very low event rate among patients who test negative and an elevated rate among the remaining patients.

In particular, for the “modified moving average” (MMA) method mentioned in a few of the public comments, not only is prospective clinical trial data missing, but there is also lacking comparison data establishing sensitivity and accuracy, published standards for interpreting the test, and an automated system for classifying the test results.

I note that the 2003 paper published in the Journal of Cardiovascular Electrophysiology (4) mentioned in one of the public comments as providing clinical support for the MMA method in fact was not a prospective study and was of a case-control design involving only 15 cases and 29 controls. Clearly this study does not come anywhere close to providing a comprehensive database for ascertaining either the positive or negative predictive accuracy of the technique.

Furthermore, a “State of the Art Paper” entitled “T-Wave Alternans and Susceptibility to Ventricular Arrhythmias” has just appeared in the Journal of the American College of Cardiology (5). On page 272 of that paper the author specifically addresses the MMA method:

“However, the promise of MMA for ambulatory TWA testing is currently limited by the absence of established diagnostic criteria. Furthermore, its sensitivity is unclear because TWA detected by MMA (25 to 100 microvolts) was an order of magnitude greater than detected spectrally (23). Prospective studies are required to compare the predictive accuracy of TWA using MMA and spectral methods.”

Once again I applaud CMS on its proposed National Coverage Decision and I look forward to the final decision leading to the wider clinical adoption of this life saving technology.

Sincerely,

Richard J. Cohen, M.D., Ph.D.

P.S. By way of disclosure, I am consultant/board member of Cambridge Heart Inc and also a consultant to Medtronic, Inc. The views expressed here, however, are exclusively my own and should be construed to represent the views of my academic employer or any other person or organization.

References:

1. Can microvolt T-wave alternans testing reduce unnecessary defibrillator implantation? Nature Clinical Practice Cardiovascular Medicine, 2005; 2, 522-528.
2. 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: 456-463.
3. 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. International Journal of Cardiology, 2005; 105, 53-57.
4. Rovere MT et al. Ambulatory electrocardiogram-based tracking of T wave alternans in postmyocardial infarction patients to assess risk of cardiac arrest of arrhythmic risk. J. Cardiovasc Electrophysol, 2003; 14:705-711
5. T-wave alternans and susceptibility to ventricular arrhythmias. J Am Coll Cardiol 2006; 47: 269-81
6. U.S. Patent #6, 735,466, 2004.

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I am an electrophysiologist, and the director of the Arrhythmia Prevention Center at the MetroHealth Campus of Case Western Reserve University.

I wish to congratulate CMS for the proposed coverage decision acknowledging the importance of further risk stratification for patients at risk for SCD.

The SCD HeFT and MADIT II study, as important as they are, have put physicians in the uncomfortable position of recommending an expensive therapy (ICD) knowing full well that only a minority will benefit from it. I have used microvolt TWA clinically to further stratify the risk of SCD in patients with LV dysfunction. In patients with a low EF, I have convinced some reluctant patients to have an ICD placed if MTWA was abnormal or reassured them if normal. I have used it in patient with significant comorbidities and/or advanced age to do the same.

My clinical practice stems from my involvement in prior and current clinical trials of MTWA that have helped better define the population at highest and lowest risk of SCD. It is clear that patients with a low EF and a normal MTWA have a negligible reisk for SCD and are likely to not benefit form the implant of an ICD. Thanks to your decision we will be able to continue ongoing trials and design new ones to use MTQA in conjunction with EF and other risk stratifiers to better define the patients who can benefit most from an ICD and, importantly those who can safely forego such an implant despite their low EF.

It should be noted that all published prospective outcome studies have been done with TWA measured during exercise (bicycle or treadmill). The importance of measuring MTWA with the spectral method and by elevating the heart rate cannot be understated. At this point, this method of measurement is the only on clinically proven to correlate with outcomes. Other methods of measuring TWA need to be subjected to rigorous, prospective scientific studies.

Like all diagnostics and therapeutics, MTWA must be reimbursed to be effectively used. Therefore, I fully support your decision to cover this test in all patients at risk of sudden cardiac death.

Sincerely,

Otto Costantini, MD
Director, Arrhythmia Prevention Center
MetroHealth Campus, Case Western Reserve University
Cleveland, Ohio

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I am writing to register my opinion that T-wave alternans (TWA) could be useful in identifying patients in sudden death and thereby may prove helpful in guiding ICD implantation in Medicare and Medicaid patients.Clearly, too many devices are being implanted unnecessarily, and there is great need to rectify this costly state-of-affairs appropriately.

However, I disagree with the proposal to use the spectral method exclusively.I was concerned that a peer-reviewed study conducted in part at our institution and published in Circulation (2004; volume 109: pages 1864-1869) using the Modified Moving Average method was not included in the literature cited in your proposed decision memorandum. This leading journal mandates careful peer review and therefore the study passed careful scrutiny. The study is relevant to ICD implantation because it was performed in ICD patients. It demonstrated that TWA is elevated in ICD patients during both mental stress and during stage 1 and peak exercise.

In addition, while the spectral method has attractive features, it is a relatively cumbersome, non-routine test that introduces perhaps unwarranted extra costs for electrodes that are particularly uncomfortable for elderly patients who have sensitive skin associated with age. Whenever possible it is important to endorse simplified technique at lower cost when the ability to predict sudden death has been documented. Unfortunately in our country the care or tests a person receives is often driven by reimbursement rather than inherent value or even the ability to provide the test at lower cost. Many good decisions by CMS in the past have been made to encourage methods that cost less and can be used on a larger group of patients. The FDA has approved both methods for obtaining information on T-wave alternans. It is rare that CMS would withhold reimbursement for a method especially when the method has been approved by the FDA and also is less expensive.

Thus, I believe that TWA is a useful clinical parameter but that limiting reimbursement to the spectral method is inappropriate and would deprive patients and their physicians of an alternative test, which can be performed cost-effectively.

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The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. The Heart Rhythm Society’s mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards. The Heart Rhythm Society’s 3,800 members are physicians, scientists and their support personnel who implant and/or follow pacemakers and implantable cardioverter defibrillators (ICDs) in patients who require these life-saving devices.

The American College of Cardiology is a 30,000 member non-profit professional medical society and teaching institution whose mission is to advocate for quality cardiovascular care—through education, research promotion, development and application of standards and guidelines—and to influence health care policy. The College represents more than 90 percent of the cardiologists practicing in the United States.

The Microvolt T-wave Alternans (MTWA) test has great potential to stratify the risk for sudden death in certain patients and may become a valuable clinical tool. There are emerging data on the usefulness of MTWA in risk stratifying patients for sudden cardiac death (SCD). However, these data do not justify requiring this test to determine which patients should or should not receive and implantable cardioverter defibrillator. There are two randomized clinical trials in progress that will assess the predictive accuracy of TWA in the ICD population and it is in this population that TWA could have an important role. The best evidence for MTWA to date is in patients with ischemic or non-ischemic cardiomyopathy, but even in these patients the evidence is not strong enough to justify its use to select patients for an implantable cardioverter defibrillator (ICD).

The Heart Rhythm Society and the American College of Cardiology believes that more prospective studies are needed to further delineate the role of MTWA in selecting patients for an ICD. Until more data are gathered and analyzed, the Society nor the College can support the routine use of MTWA in selecting patients for an ICD or making this test a required element of the National ICD Registry.

We support CMS’ decision not to require the MTWA test as a prerequisite to ICD placement. HRS and the ACC believe that MTWA is one of several diagnostic tools a physician may find useful in evaluating a patient at risk for sudden cardiac death and determining the best therapy for that patient. Selection of the diagnostic tools most appropriate for each patient’s individual circumstances should be left to the treating physicians’ judgment. We are pleased that CMS’s proposed coverage decision for the MTWA test will support this important physician decision making.

We are thankful for CMS’s continued willingness to work cooperatively with the physician community to develop reasonable and effective coverage policies for Medicare program. Our objective is the same as that of CMS, to ensure that Medicare coverage decisions are based on sound clinical judgment and the best objective scientific evidence currently available.

Thank you very much for your consideration of these comments.

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I wanted to comment on how valuable this mode of testing has been for my practice. I am a cardiologist in a rural area and nearly a 100 miles from the next “big” medical center. I see a large number of patients that are older and don’t either have the capacity or the means to go a 100 miles unless it is absolutely necessary. T wave alternans allows me to risk stratify those patients who are at high risk and therefore must be further studied and need to be convinced to make the arduous journey. Since its use, it has provided me with invaluable insight allowing me to provide treatment prior to what may have otherwise been a fatal dysrhythmia.

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The microvolt TWA measurement by spectral analysis method as afforded by Cambridge Heart instruments has now withstood the test of time. Different trials involving at risk populations of both ischemic and nonischemic cardiomyopathy have elucidated a good discriminatory power for the test in terms of risk stratification for sudden death. The test is easy to use, with an easy learning curve for application and interpretation and is thus widely applicable. The discriminatory value supercedes that of programmed ventricular stimulation (PES) particularly in nonischemic cardiomyopathy patients. Furthermore, the said test remains a safer alternative than PES where potentially lethal ventricular arrhythmia is an endpoint.

Although a depressed EF is currently accepted as a risk stratifier, there is concern that the number of patients treated compared to life/years saved remains high, with a high cost to society. Further risk stratification appears necessary and MTWA is well suited for that.

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Guidant Corporation welcomes the opportunity to comment on the Centers for Medicare and Medicaid Services’ (CMS) national coverage analysis regarding Microvolt T-wave Alternans, CAG – 00293N.

Headquartered in Indianapolis, Indiana, with manufacturing and/or research and development facilities in the states of Minnesota, California and Washington, as well as in Puerto Rico and Ireland, Guidant Corporation is a leading designer and manufacturer of medical technologies used primarily to treat cardiovascular and vascular illnesses. Guidant's products save and enhance lives.

As a proud sponsor of evidence-based medicine, Guidant supports the continuing drive to stratify risk and effectively assess which patients benefit most from life-saving ICD therapy. Microvolt T-Wave Alternans (MTWA) diagnostic testing technology as a method of identifying low-risk patients who are less likely to benefit from ICD therapy appears to be promising; as such, Guidant supports the science that Cambridge Heart and other manufacturers are currently undertaking to address this question. We also believe more data needs to be acquired, analyzed, and peer-reviewed on MWTA in ICD-indicated populations, and that we need to better understand the enduring impact of this diagnostic test. Additionally, we’re concerned for the long-term welfare of patients who initially test MTWA normal/negative and either suffer a life-threatening arrhythmia or are not retested again in the future.

Guidant would like to share a careful observation regarding this decision. We agree that MTWA could be a potentially useful technology to stratify patients, yet we want to ensure that the level of clinical evidence needed for national coverage determinations is consistent. It is important for CMS to set predictable, documented evidence standards that are public, transparent, and well understood by all parties involved. The most recent NCDs, such as this, are often viewed as the precedence for the quality and evidence standards upon which CMS bases future decisions.

Gehi et al recently published a meta-analysis in the Journal of the American College of Cardiology that focused on the predictive value of using MTWA risk stratification for ventricular tachyarrhythmia in multiple populations. The authors came to the conclusion that the test has significant predictive value, but yet has limitations to its use, particularly depending upon which population is being evaluated. They go on to say that the “predictive value of MTWA when used with other methods of risk evaluation is unclear”.[i]

The MTWA test might have a negative predictive value (NPV) for the ICD-indicated Medicare population that is lower than the 97% number Gehi et al states. When looking closer at the individual trials in this analysis, it becomes apparent that many were not done in ICD-eligible populations. Additionally, some were performed in quite healthy populations, (one-third of the studies in the meta analysis with reported ejection fractions (EF) had an average EF of >50%)[ii] thus calling into question the true NPV, which is potentially lower. As a result, many Medicare beneficiaries could miss being referred on to an Electrophysiologist for further testing and evaluation. Guidant wants Medicare beneficiaries at risk for SCD and other cardiac illnesses to receive full consideration for ICD therapy, and not be turned away based just on the results of one simple test. In other words, the combination of a lower NPV and fewer patients potentially being referred to Electrophysiologist for evaluation could equate to more people “falling through the cracks”.

Guidant is especially concerned for the long-term well-being of patients who test negative, as there is a lack of data showing what happens to them 20 months post-MTWA test; science has not yet proven that the results would be the same if given the T-wave test again in the future. Even Cambridge Heart bounds the time for which the results are applicable, suggesting, “Patients in these groups who have a normal MTWA test are not likely to experience a sudden cardiac event for 1-2 years, and therefore not likely to benefit from ICD therapy.”[iii] Additionally, they go on to mention, “…negative patients should be re-tested every 12 months, as cardiac function can change over time.”[iv] The number of people who test negative could be considerable, and if physicians do not fully educate their patients about the need to re-test, they could be at risk for missing a change in cardiac function, and thus potential for serious illness or death.

Blue Cross and Blue Shield Technology Evaluation Center also released an assessment titled, “Microvolt T-Wave Alternans Testing to Risk Stratify Patients Being Considered for ICD Therapy for Primary Prevention of Sudden Death” in October 2005. That assessment concluded, “that the evidence is insufficient to determine whether the use of MTWA improves net health outcomes or whether it is as beneficial as any established alternatives.”[v] Additionally, the findings concluded that the health outcomes were not established in investigational settings, again prompting BCBS to come to the overall conclusion that, “the use of microvolt T-wave alternans testing for risk stratifying patients being considered for implantable cardioverter defibrillator therapy for primary prevention of sudden death does not meet the TEC criteria.”[vi]

A majority of evidence referred to in the TEC assessment included patients that do not meet eligibility requirements for ICDs [vii], and as such, it would be difficult to compare how effective MTWA would be in primary prevention device-indicated patients.

Medtronic and St. Jude Medical both have significant, well-designed trials underway that use MTWA as a risk stratification tool to show which primary prevention patients might be most likely to benefit from ICD therapy. Additionally, Guidant has a large observational study in progress in Italy. There currently is a lack of prospective, randomized, controlled trials with peer-reviewed articles for MTWA, and these studies will provide more clarity and transparency to this topic. In the meantime, physicians will have to make decisions on the use and interpretation of this test based on careful consideration of the available clinical evidence.

We appreciate the opportunity to comment, and look forward to continuing to work with CMS in the future.

[i] Gehi AK, Stein RH, Metz LD, Gomes JA. Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events: a meta-analysis. J Am Coll Cardiol. 2005 Jul 5; 46 (1): 75-82.

[ii] GehiAK, Stein RH, Metz LD, Gomes JA. Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events: a meta-analysis. J Am Coll Cardiol. 2005 Jul 5; 46 (1): 75-82.

[iii]Cambridge Heart website, frequently asked questions, “What Role Does MTWA Testing Play in a SCD-Heft or MADIT II Patient?” Available at:http://www.cambridgeheart.com/content/Shared/FAQ.shtml#q8 Accessed January 11, 2006.

[iv]Cambridge Heart website, frequently asked questions, “What do I do if my patient tests MTWA negative/normal?” Available at: http://www.cambridgeheart.com/content/Shared/FAQ.shtml#q8 Accessed January 11, 2006.

[v] Blue Cross Blue Shield Association TEC. Microvolt T-Wave Alternans Testing to Risk Stratify Patients Being Considered For ICD Therapy for Primary Prevention of Sudden Death. Assessment Program, Volume 20, Number 9. October 2005. Available at: http://www.bluecares.com/tec/vol20/20_09.html.Accessed January 11, 2006.

[vi]Ibid.

[vii]Blue Cross Blue Shield Association TEC. Microvolt T-Wave Alternans Testing to Risk Stratify Patients Being Considered For ICD Therapy for Primary Prevention of Sudden Death. Assessment Program, Volume 20, Number 9. October 2005. Available at: http://www.bluecares.com/tec/vol20/20_09.html.Accessed January 11, 2006.

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Medtronic, Inc. is the world’s leading medical technology company specializing in implantable and interventional therapies that alleviate pain, restore health, and extend life. We are committed to research and development necessary to produce high quality products and to support innovative therapies that improve patients' lives. We appreciate the opportunity to comment on the Proposed National Coverage Determination (NCD) for Microvolt T-wave Alternans (MTWA).

Medtronic supports the further evaluation of risk-stratification technologies based on sound clinical evidence to ensure appropriate utilization of ICD therapy. To that end, Medtronic continues to explore a number of methods of risk stratification including proteomics and genomics, in addition to our evaluation of MTWA. Medtronic is currently sponsoring the MASTER Trial of over 1,000 patients, in conjunction with the requestor Cambridge Heart, and supports local Medicare coverage for MTWA.

Medtronic agrees with much of the discussion in the proposed NCD regarding the potential of MTWA. We also support and agree with CMS’ statement that the current evidence is not sufficient to require that physicians use the results of MTWA testing to select appropriate patients for ICD implantation. Mandating a prerequisite test for risk stratification should always require the risk stratification technology to possess the same level of evidence as the procedure itself. In the case of ICDs, the strength of the evidence, established through randomized controlled trials, is substantially larger and more robust than the current level of evidence for MTWA.

Given the current level of evidence for MTWA, Medtronic is somewhat surprised by the breadth of the proposed national coverage decision. There are several questions that remain unresolved related to MTWA testing. The first of these involves how clinicians should handle situations where patients may not be appropriate candidates for MTWA testing. This includes patients with atrial fibrillation, prolonged QRS complexes (Rashba et al. 2002), premature ventricular contractions (PVCs) or those unable to reach an adequate heart rate for testing, the latter being a serious concern, particularly for an elderly heart failure population. If CMS proceeds with a national coverage decision, some recognition of these limitations should be added to the one line national coverage decision being proposed.

Another question related to MTWA is how frequently the test should be performed to effectively safeguard primary prevention patients from SCD. There is an absence of long term data regarding the outcomes for patients who have initially tested MTWA negative, and therefore, the duration of the validity of a negative test is uncertain. One study with longer term follow-up reported an overall event rate of 13% over 52 months in patients with a negative MTWA (Grimm et al. 2003). In that study, the first recorded events occurred in less than 12 months following a negative test. Given these results and the progressive nature of cardiovascular disease, it is uncertain how frequently clinicians should repeat the testing to ensure the safety of their primary prevention patients. If clinicians must perform frequent and repeated testing to determine the point at which their patients may be at suitable risk for an ICD, cost effectiveness, which is at the heart of this proposed national coverage policy, may never be realized.

Finally, the MTWA policy is much broader than the current Medicare ICD coverage policy. This will present an issue for physicians who encounter a patient, who tests MTWA positive, but their ejection fraction is over 35% and therefore, the patient is considered ineligible for ICD therapy under CMS’ NCD for ICDs.

Thank you for the opportunity to comment.

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St. Jude Medical, Inc., a developer, manufacturer, and a distributor of innovative medical devices including implantable cardioverter defibrillators (ICDs), appreciates the opportunity to comment on the proposed National Coverage Decision Determination (NCD) for the use of Microvolt T-wave Alternans (MTWA).

The literature has identified MTWA as a promising predictor of ventricular arrhythmias and sudden cardiac death (SCD), and as such, a potential risk stratification tool for identifying those patients most likely to benefit from ICD therapy. In July 2005 CMS opened a National Coverage Analysis (NCA) to determine if the evidence supports the use of MTWA for the evaluation of Medicare beneficiaries at risk for SCD. St. Jude Medical’s response stated that while there is evidence that MTWA testing may be a predictor of ventricular arrhythmias and sudden cardiac death in certain groups of at-risk patients, the available evidence is insufficient to require MTWA testing prior to ICD implant or to withhold ICD therapy on the basis of MTWA test results. We noted that several large studies examining the predictive value of MTWA in populations eligible for ICD therapy are already in progress, including the Alternans Before Cardioverter Defibrillator (ABCD) clinical study sponsored jointly by St. Jude Medical and Cambridge Heart, which may provide more definitive information concerning the value and limitations of MTWA in guiding therapy in the ICD primary prevention population. We recommended that the NCA by delayed until data from these ongoing studies are available (mid-to-late 2006) and that coverage continue under the local authority.

In its proposed January 7, 2006 decision memo, CMS has determined that there is sufficient evidence to provide standard national coverage of this technology for the evaluation of Medicare beneficiaries at risk for SCD, although the quality of evidence is inadequate to conclude MTWA testing can improve net health outcomes for Medicare patients who are candidates for ICD placement. We agree that the use of MTWA may enhance risk stratification for SCD; we also concur that the evidence is not sufficient to justify its use to select patients for ICD therapy. In fact, based on the evidence available in the published literature, it is premature to advocated the widespread use of any single non-invasive technique to risk-stratify patients being considered for ICD therapy without further study and confirmation in prospective trials. Further, CMS expanded ICD coverage for the MADIT II and SCD-HeFT patient populations based on extensive and definitive clinical data. Coverage for these patient populations should only be expanded or contracted on the basis of equally extensive and definitive clinical data.

MTWA is a promising technology: however, there are several clinical limitations and unresolved questions concerning its use:

• MTWA cannot be assessed in patients with atrial fibrillation, prolonged QRS complexes, significant ventricular ectopy (frequent PVCs), or in patients who cannot exercise to reach 85% maximum cardiac output, which not infrequently occurs in an elderly, heart failure population. These limitations to MTWA testing could result in up to half of the primary prevention ICD populations being non-indicated for MTWA testing.

• There are no prospective clinical studies as yet designed and underway or completed with data published demonstrating improvement in outcomes among patients selected for implantable cardioverter/defibrillator therapy based on the results of T-wave alternans testing.

• White MTWA testing is useful in evaluating the risk for ventricular arrhythmias in certain high risk patients, the predictive value of T-wave alternans in much larger populations requires study and confirmation in prospective trials.

• The reproducibility of the MTWA test under circumstance of alterations of patients’ pharmacologic therapy or physiologic substrate changes over time still requires clarification.

• The frequency of testing need to determine when and under what circumstances a MTWA negative patient should be retested to evaluate if the patient has converted to MTWA positive has not been clearly elucidated.

• Much of the data evaluating MTW includes a lower risk population of patients (i.e., EF > 35%) and many of those patients are not currently covered for ICD therapy.

Further studies may establish MTWA as an integral part of risk stratification for SCD and define its role in patients indicated for ICD therapy.

We thank you for the opportunity to provide comments and look forward to continuing to work with you on these important issues.

Sincerely,

Susan Walker
Directory, Reimbursement

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I feel strongly that the use of T wave alternans testing can help determine which patients who are candidates for ICD implantation are at greatest risk for sudden cardiac death. Because it has a very good negative predictive value, a negative test provides reassurance to both the patient and physician that ICD implantation is unlikely to provide additional mortality benefit. Thus, it saves the patient the risk and expense of an invasive procedure and the associated long-term complications. I use T wave alternans testing routinely in my practice to help determine which patients do not need ICDs. It is my anecdotal observation that many patients with positive tests who subsequently undergo ICD implantation will return with appropriately delivered shocks from their defibrillator for potentially fatal ventricular arrhythmias. It is my opinion that ANY patient with a NEGATIVE test should NOT undergo ICD implantation, while those with POSITIVE tests should have ICDs implanted.

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I am writing to support the CMS's draft decision to provide national coverage for microvolt T-wave alternans (MTWA) testing.

I have been the author of many papers that involve the use of MTWA in risk-stratifying patients susceptible to ventricular tachycardia and sudden cardiac death, including two major review articles (references 6 and 8 below):

1. Esperer HD, Armoundas AA, Rosenbaum DS, HU Klein, Cohen RJ. Specificity of T-wave alternans in individuals without organic heart disease who are not inducible during ventricular programmed stimulation. G Ital Cardiol 28 (suppl 1): 95-97, 1998.

2. Armoundas AA, Rosenbaum DS, Ruskin JN, Garan H, Cohen RJ. Prognostic Significance of Electrical Alternans Compared to Signal Averaged Electrocardiography in Predicting the Outcome of Electrophysiologic Testing and Arrhythmia-Free Survival. Heart 80: 251-256, 1998.

3. Armoundas AA, Osaka M, Mela T, Rosenbaum DS, Ruskin JN, Garan H, Cohen RJ. T-wave Alternans and Dispersion of the QT Interval as Risk Stratification Markers in Patients Susceptible to Sustained Ventricular Arrhythmias American Journal of Cardiology 82: 23-25, 1998.

4. Armoundas AA, Nanke T, Cohen RJ. T-Wave Alternans Preceding Torsades de Pointes Ventricular Tachycardia, Circulation 101: 2350, 2000.

5. Armoundas AA, Cohen RJ. Clinical Utility of T Wave Alternans. Cardiac Electrophysiology Review 1 (3): 390-394, 1997.

6. Armoundas AA, Tomaselli GF, Esperer HD. Pathophysiologic Aspects and Clinical Relevance of Repolarization Alternans: Current Status and Perspectives. Journal of the American College of Cardiology 40(2): 207-17, 2002.

7. Armoundas AA, Albert CM, Cohen RJ, Mela T. Utility of Implantable Cardioverter Defibrillator Electrograms to Estimate Repolarization Alternans Preceding a Tachyarrhythmic Event. J Cardiovasc Electrophysiol, 15(5):594-7, 2004.

8. AA Armoundas, S Hohnloser, T Ikeda, RJ Cohen. Can Microvolt T-Wave Alternans Testing Reduce Unnecessary Defibrillator Implantation? Nat Clin Pract Cardiovasc Med, 2(10): 522-8.

We have recently shown (reference 8 above) that in populations of patients similar to those studied in MADIT II or SCD-HeFT (patients with a history of ischemic or non-ischemic heart disease and reduced ejection fraction who were not selected on the basis of a prior history of VT/VF) that the average annual rate of fatal and nonfatal ventricular tachyarrhythmic events among the patients who test negative for TWA is approximately 1% per year. This rate is so low that it is unlikely that such patients would benefit from ICD therapy. Moreover, the mortality among such patients who test negative for TWA is substantially lower than that observed in the MADIT II and SCD-HeFT trials for patients who received ICDs, suggesting that a negative TWA test alone in those patients is a strong indication that the probability of experiencing a tachyarrhythmic event is very low.

Besides the analytic spectral method, several other methods have been applied for detection and quantification of TWA, such as autocorrelation, complex demodulation, and autoregression techniques. Given the fact that one of the inherent strengths of the analytic spectral method is its ability to differentiate between true alternans and non-specific noise in the ECG, I find that it is appropriate that further investigation is needed to show that these alternative methods are clinically equivalent to the analytic spectral method. Furthermore, given that the analytic spectral method is the only method that has been validated by a wide range of prospective studies, I believe that coverage should be limited to the analytic spectral method.

Finally, noise is a significant co-founding factor in this very sensitive ECG analysis. Accordingly, multi-electrode noise-reducing sensors have been uniformly employed in the studies which prospectively validated the clinical efficacy of this method. Accordingly, I believe that use of noise-reducing multi-electrode sensors should be required for CMS coverage of the test.

Sincerely,

Antonis Armoundas, PhD

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I am writing to strongly support the proposed NCD regarding MTWA testing for patients at risk for sudden cardiac death.

I am Associate Director of Cardiac Electrophysiology at the Weill Medical College of Cornell University and have extensive clinical and research experience with TWA testing. I agree wholeheartedly with the evidence-based conclusions that: 1)"MTWA is a useful risk stratification tool" and that there is strong evidence suggesting that patients with normal MWTA studies are at low risk of sudden death, and 2) that "the evidence is sufficient to show that MTWA should be the only diagnostic test for the purpose of stratifying high risk patients of VTE."

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My practice has been doing MTWA testing for 2 years and I am extremely pleased with the sensitivity of this diagnostic test. I am an interventional cardiologist and my practice does nuclear stress testing in our imaging center and soon will be doing CT angiography. We consider ourselves to be very progressive and have icorporated MTWA testing into our pactice. I am a strong advocate for this essential diagnostic test and feel that it should be covered nationally so more people can benefit from this technology.

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The data on MVTW alternans have been building for years, and at present the test seems very reasonable to use for risk-stratification. Its false-negative rate is very low, and I can imagine situations where a negative test could be useful. For example, in an ICD recall situation, a negative MVTW alternans test would suggest that a borderline patient would be a reasonable candidate for observation in lieu of device replacement. I do not think the data are sufficient to use the test to exclude patients from receiving an ICD, but in some patients MVTW results may help in the decision on whether to implant an ICD.

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Great Lakes Heart and Vascular Institute in St. Joseph Michigan has been utilizing the Microvolt T wave Alternans test for approximately 2 years now. We initially started using the test for a Medtronic sponsered Masters Study. We have found this test useful for several situations. One situation that has occured is using the test to help convince skeptical patients about their high risk for sudden death when the patient already meets Madit II criteria. We also use it in patients that have slightly higher EF's with unexplained syncope or frequent ectopy on EKG's, stress tests or Holters. In summary we feel that Micro T wave Alternans testing is very helpful and would benefit more people with a broader range of coverage for patients thought to be at high risk of sudden death.

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As an engineer, software designer, and inventor, I am pleased that CMS is proposing to approve national coverage for T-wave Alternans (TWA) as a parameter for evaluating risk for sudden cardiac death. However, I think that it is not appropriate to exclude the use of the Modified Moving Average method and to restrict coverage only to the spectral analytic method.

This view is based on considerable evidence regarding signal processing principles, and basic and clinical scientific evidence, which indicate that the two approaches are substantially equivalent. Both methods have been shown to share the following performance characteristics and capacities:

1) Capability to measure TWA with 1-microvolt accuracy and resolution:From an engineering perspective, both the Cambridge Heart spectral method and the GE modified moving average method have been tested and shown to be capable of measuring microvolt levels of TWA (FDA K032513; Nearing and Verrier 2002, listed under point 5 below).

2) Equivalent capabilities to remove baseline wander and to reduce noise: The specialized electrode approach that Cambridge Heart uses is one way to reduce thermal noise and baseline wander from the ECG signal, but this objective can also be achieved by signal processing techniques. The GE system employs several highly advanced signal-processing techniques, including cubic spine correction and a cubic alignment filter. An advantage of MMA is that it achieves the same level of correction while circumventing the need for costly one-time use of consumable electrodes, which add approximately $100.00 to the cost of every test performed. At our hospital alone, 8000 exercise tests are performed annually. If only half the tests were for TWA a cost of $400,000 to our institution alone. On a national scale, this cost would represent a staggering expenditure. Clearly, the use of software for noise reduction, as offered by the GE system, allows tremendous savings at no loss of accuracy.

3) Both methods can uncover risk for sudden death by quantifying the same electrophysiologic entity, namely, TWA: The Cambridge Heart system relies on generating a beat spectrum, assuming that the ABAB pattern repeats itself on an every-other beat basis, namely at 0.5 cycles/beat. The spectrum, although accurate, unfortunately eliminates the opportunity for the user to inspect the ECG morphology. With the GE system, the ABAB pattern is understood to represent two populations of beats, namely “A” and “B” forms. A moving average generates a representative template of the “A” and “B” forms. The magnitude of the TWA is measured as the maximum difference of the A and B forms during the T wave. The major advantage of this approach is that the ECGs can be inspected, and the differences between the “A” and “B” forms during the T wave can be verified visually to a level as low as 20 microvolts, with the aid of superimposition. Detailed testing of the algorithms has revealed a correlation in TWA magnitude readings between the spectral analytical method and the MMA method at 0.98 and 0.99, with and without noise, respectively.

4) Both methods take advantage of the capability to expose TWA during conditions with elevated heart rates associated with exercise:The Cambridge Heart system requires elevating the patients’ heart rates to 105 to 110 beats/min during exercise and maintaining their heart rate constant within this target zone in order to generate a spectrum. The inability to achieve this heart rate control contributes to the 20 to 30% of indeterminate tests. In contrast, the GE system uses the more dynamic modified moving average approach, can accurately determine TWA every 15 seconds, and does not require the patient to “lock in” on a target rate since this “time-domain” method does not have the limitation of requiring data stationarity. Thus, the GE system reduces the likelihood of indeterminate test results that may be associated with inability especially in older patients to perform what can be a demanding exercise test.

5) As with the spectral analytic method the Modified Moving Average method has shown the utility of TWA analysis in patients at risk for sudden death in peer- reviewed literature:

Nearing BD, Verrier RL. Modified moving average method for T-wave alternans analysis with high accuracy to predict ventricular fibrillation. Journal of Applied Physiology 2002;92:541-549.

Verrier RL, Nearing BD, LaRovere MT, Pinna GD, Mittleman MA, Bigger JT, Schwartz PJ for the ATRAMI Investigators. Ambulatory ECG-based tracking of T-wave alternans in post-myocardial infarction patients to assess risk of cardiac arrest or arrhythmic death. Journal of Cardiovascular Electrophysiology 2003;14:705-711

Kop WJ, Krantz DS, Nearing BD, Gottdiener JS, Quigley JF, O’Callahan M, Delnegro AA, Friehling TD, Karasik P, Suchday S, Levine J, Verrier RL. Effects of acute mental and exercise stress on T-wave alternans in patients with implantable cardioverter defibrillators and controls. Circulation 2004;109:1864-1869.

Sincerely,

Bruce D. Nearing, Ph.D.
Assistant Professor of Medicine, Harvard Medical School Cardiology Division, Beth Israel Deaconess Medical Center
Co-inventor of the Modified Moving Average approach to TWA measureme

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I support the decision to extend coverage for MTWA testing in all MADIT II/SCD-HeFT eligible patients. The excellent negative predictive value in this patient population provides an effective method for identifying patients at low risk who may not require ICD implantation, and a rational approach for containing health care costs. Moreover, recent data suggests that prophylactic ICD implantation in MTWA negative MADIT-II type patients may not be clinically effective, and certainly not cost effective. As such, use of MTWA in such patients should be encouraged by Medicare.
Regards,
Theodore Chow MD
Electrophysiology, Ohio Heart & Vascular Center
Principal Investigator, MASTER Trial

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This comment is provided in response to the request for public comment regarding the pending decision to approve Microvolt T-wave Alternans testing (MTWA) as a useful technique for sudden death risk (SCD) stratification. My opinions are based on approximately 25 years of clinical experience caring for patients believed to be at high risk of SCD employing various 'risk stratification' strategies, and more recently as a principal investigator and participant of a multicenter trial evaluating MTWA.

First, given both the clear need for improving methods of assessing SCD risk, and the extensive existing clinical experience and supporting literature concerning MTWA methodology, I fully concur with the CMS proposal to support coverage for MTWA testing. I am confident that more widespread use of MTWA will enhance patient care by better identifying those individuals at relatively lower SCD risk from a pool of patients with comparable underlying disease, ECG findings, and ejection fractions.

Second, I believe that MTWA will permit more efficient use of limited health care resources, by reducing application of implantable cardioverter defibrillator (ICD) therapy in relatively ower risk patients and instead focusing our efforts on a subset of individuals in seemingly greater need. On the other hand, I think it inappropriate to restrict reimbursement for MTWA testing to a single methodology (the spectral analytic method). Other approaches such as the Modified Moving Average Method have been deemed effective and have been approved by the US Food and Drug Administration (FDA, reference below). These other methods, each thoroughly assessed and having received sufficient scientific scrutiny to meet FDA standards would not receive equitable treatment from payors. Physicians , clinics, and manufacturers who have spent considerable time, effort, and financial resources to develop and apply these apparently effective alternative methods would be treated unfairly by the proposed methodologic restriction. The CMS commentary suggests that peer-reviewed publications supporting algorithms other than spectral analysis were not available. Consequently it was concluded that current evidence only supports the spectral analysis approach. However, subsequent findings have been published showing the effectiveness other MTWA detection methods, and the FDA has agreed.

FDA has approved the Modified Moving Average Method available in General Electric's (GE) system. This Modified Moving Average Method has been deemed substantially equivalent to the spectral analytic method. Therefore, the clinical results derived from either technique should be comparably applicable in the clinical decison-making process. Thus, it would be inappropriate to focus approval for reimbursement on only one method.

Limiting the decision to a single method (a proprietary product distributed by one manufacturer), when other approaches have been deemed medically equivalent after extensive regulatory review by the FDA, reduces the possibility of competition, and limits physician access to potentially cost effective technologies.

In my view, while strongly favoring reimbursement for MTWA, I urge CMS to reconsider that aspect of its decision that limits coverage to one proprietary methodology. Coverage should be provided for any MTWA detection system that has met the clearly rigorous standard of FDA approval.

I very much appreciate your careful consideration of this comment.

Reference
The FDA clearance document (K032513) for GE Medical System's ECG analysis algorithm

Potential Conflicts of Interest Disclosure
The author is a consultant to Medtronic Inc., St Jude Medical Inc., Transoma Inc., manufacturers of implantable medical devices.

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I hope that MTWA is going to be an integral part of the decision making process in my practice over the foreseeable future. It is noninvasive and easy to perform. I am impressed by the negative predictive value that will allow me to better risk stratify both ischemic and nonischemics. Furthermore, I practice in a sophisticated community, and especially in patients who meet MADIT 2 or ScDHeFT criteria but have not had an arrhythmic event, an abnormal study will allow me to provide the patient with objective evidence that they have at least a four-fold greater risk of an arrhythmic event to be able to make an informed decision. I would enthusiastically endorse a national coverage policy.

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Not every patient with poor Left Ventricular Function requires an implantable cardioversion device (ICD), and the Microvolt T-Wave Alternans (MTWA) aids in identifying those patients that are high risk. Recent trials have shown that only 20% of all ICD firings are appropriate. There is no doubt that MTWA would increase the percentage of appropriate ICD firings by creating a more accurate patient selection, thus saving lives in a more cost effective manner.

The negative predictive value is the most valuable tool in identifying the most appropriate patient for electrophysiology testing and ICDs. It is through this data and I strongly urge your plan to approve coverage and reimbursement for Microvolt T-Wave Alternans testing.

Thank you,

Dr. Pradip Jamnadas, MD, MBBS, FACC, FSCAI, FCCP,
FACP
Cardiovascular Interventions, P.A.

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I applaud CMS for their consideration regarding the potential re-imbursement for Microvolt T-wave alternans. I believe the data reported are excellent and by utilizing this technology we can reduce the risk of SCD, and actually save our health care resources as we look to better identify those patients who are high risk.

I agree with many of my colleagues, when I point out that I am very troubled regarding some of the language in the proposed decision memo. By restricting reimbursable testing to the spectral method only, CMS is excluding other current modalities such as the Modified Moving Average method. Perhaps more importantly, this decision will likely restrict the development of new technology which will have the anticipated effect of protecting market share for the method developed and utilized solely by Cambridge Heart. With free market forces restricted, there will likely be fewer investigations exploring other modalities, less innovation and therefore less progress regarding a potentially cheaper and perhaps more accurate method.

I therefore propose that the sentence, "We propose to issue a National Coverage Determination (NCD) that states: Microvolt T-wave Alternans diagnostic testing is covered for the evaluation of patients at risk of sudden cardiac death, only when the spectral analytic method is used" be amended to include other current and perhaps future modalities.

Thank you for your consideration.

Jonathan Sheinberg. MD FACC
Texas Cardiovascular
Austin, TX

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I am a Canadian clinical electrophysiologist with a research interest in device therapy for patients at risk of sudden death. It is clear that the identification of patients at risk for sudden death via noninvasive methods is necessary in order to better identify those who might benefit from a prophylactic implantable defibrillator. Although the decision of CMS will not directly affect my practice, it will profoundly impact the lives of tens of thousands of patients in the United States. I applaud the CMS for taking the initiative to expand the indication for microvolt T wave alternans (MTWA) testing. Spectral MTWA has been shown to be useful in identifying patients with chronically depressed ejection fractions who are at risk for life-threatening arrhythmias. The most convincing evidence is that of Bloomfield and colleagues (J Am Coll Cardiol 2006;47:456-63) who found that the absence of MTWA is associated with a good prognosis(2.5% 2 year event rate).

I have a considerable experience with spectral MTWA, having personally performed over 800 assessments. As with any noninvasive technique, spectral MTWA has limitations. It requires patients to be in sinus rhythm, be able to maintain a heart rate of 105-110/minute, and is limited by excessive noise and ventricular ectopy. There is also insufficient data on the utility of MTWA in patients with recent onset heart failure or those who have survived a recent myocardial infarction. As pointed out by others, there is limited data on non-spectral methods of MTWA assessment. While these methods hold promise, I believe that they should be considered as research tools until such prospective data are available. Other risk assessment methods have also been studied and show promise. These include, but are not limited to, baroreceptor sensitivity (Lancet 1998;351:478-84) and heart rate turbulence (Lancet 1999;353:1390-6).

My comments are not meant to detract from the clear value of spectral MTWA in select patients. I have simply voiced my opinions to provide additional perspective.

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We believe that T wave alternans analysis is a valuable clinical tool and should be compensated by CMS. Although initial studies are promising, the clinical utility of this test remains to be confirmed in large randomized trials in patients with severely depressed LVEF. In this patient population numerous large randomized trials have proven the efficacy of the implantable defibrillator, and more evidence is needed before this treatment modality is abandoned for a subset of this group.

The present value of the test lies in the risk assessment of patients in whom treatment indications are not clear: eg, the patient with les severe LV dysfunction (LVEF>35%), or unusual presentations, ie asymptomatic SCN5 mutation carriers etc.

It is quite conceivable that T wave alternans may eventually prive to be an excellent risk stratifier in severe LV dysfunction, but more data is needed before a proven therapy is discarded; and the quality of the data must be similar to that available for presently accepted therapy (the ICD)

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This comment is intended to convey my support for CMS’s decision to recommend coverage for TWA testing for sudden death risk stratification. I am writing to provide peer-reviewed evidence of the accuracy and clinical value of Modified Moving Average method of TWA analysis in order to address a gap cited on page 14 of the proposed decision memorandum. Given the information below, it would be inappropriate to exclude coverage for the Modified Moving Average approach for TWA analysis. ]

In 1991, my colleague Dr. Bruce Nearing, a signal-processing engineer, and I published in Science one of the first articles to demonstrate proof of the principle that quantification of T-wave alternans (TWA) could be of value in assessing risk for sudden cardiac death (1). We used the spectral method of complex demodulation. Subsequently, our group and others provided evidence in the medical literature supporting the electrophysiological basis for the predictive capacity of this fundamental phenomenon (2,3).

However, we recognized that spectral methods have important intrinsic limitations, as they require the patients’ heart rate to be stable in order to develop a continuous regular beat stream. Because we appreciated that heart rate changes dynamically, we sought a method that would allow us to monitor TWA during real-life conditions. With this feature in mind, we developed the time-domain Modified Moving Average method, which draws on the powerful capacity of recursive averaging by successive templates to reject noise. The engineering validation and experimental evidence of MMA’s suitability to measure TWA accurately under clinically relevant conditions involving noisy signals and abrupt changes in heart rate were published in a leading peer-review journal in 2002 (4). Our results were independently verified by extensive testing of the MMA signal processing approach by Martinez and Olmos (5) and Shusterman and Goldberg (6) in peer-reviewed journals. GE Healthcare licensed the Modified Moving Average method and, drawing on their many years of experience with clinical recordings, developed additional noise-reduction software. The FDA has cleared the performance of the algorithms to an accuracy and resolution of 1 microvolt and indicated, “GE’s TWA algorithm measurements have been found to be predictive of arrhythmic death and can be used for the purpose of risk stratification” (K032513).

In addition to laboratory studies, we have tested the predictive power of TWA assessed by the Modified Moving Average analysis in ambulatory patients recovering from myocardial infarction during daily activities and published our findings in a peer-reviewed study (7). In a multicenter study, an investigator blinded to clinical outcome analyzed the data according to prestated hypotheses. Thus, the analysis was prospective and not retrospective, as has been suggested. The study controlled for clinical characteristics and standard risk factors including age, gender, site of MI, thrombolysis, beta-blockade, and left ventricular ejection fraction. We found a statistically significant capability to predict arrhythmic death or cardiac arrest across the two-year followup even in these relatively low-risk post-myocardial infarction patients. These results carry important implications as the study group is representative of a sizable population in whom improved risk arrhythmia assessment is greatly needed.

The capacity of MMA to assess risk in ICD patients during exercise as well as mental stress was evaluated in a peer-reviewed study published in Circulation (8). More recently, Shusterman and Goldberg demonstrated, using an algorithm similar to MMA, that an upsurge in the magnitude of TWA immediately precedes the onset of ventricular tachycardia (9). This finding confirms our peer-reviewed experimental study published in Circulation Research (10).

In summary, there is substantial peer-reviewed evidence of the accuracy of the MMA method in quantifying TWA for sudden death risk stratification. Thus, I do not believe that it is appropriate to exclude the MMA method from CMS coverage. The restriction of coverage to the spectral analytical method should be deleted.

References:

1. Nearing BD, Huang AH, Verrier RL. Dynamic tracking of cardiac vulnerability by complex demodulation of the T-wave. Science 1991;252:437-440.

2. Verrier RL, Nearing BD. Electrophysiologic basis for T-wave alternans as an index of vulnerability to ventricular fibrillation. Journal of Cardiovascular Electrophysiology 1994;5:445-461.

3. Armoundas AA, Tomaselli GF, Esperer HD. Pathophysiological basis and clinical application of T-wave alternans. Journal of the American College of Cardiology 2002;40:207-217.

4. Nearing BD, Verrier RL. Modified moving average method for T-wave alternans analysis with high accuracy to predict ventricular fibrillation. Journal of Applied Physiology 2002;92:541-549.

5. Martínez JP, Olmos S. Methodological principles of T wave alternans analysis: A unified framework. IEEE Transactions on Biomedical Engineering 2005;52:559-613.

6. Shusterman V, Goldberg A. Tracking repolarization dynamics in real-life data. Journal of Electrocardiology 2004;37;180-186.

7. Verrier RL, Nearing BD, LaRovere MT, Pinna GD, Mittleman MA, Bigger JT, Schwartz PJ for the ATRAMI Investigators. Ambulatory ECG-based tracking of T-wave alternans in post-myocardial infarction patients to assess risk of cardiac arrest or arrhythmic death. Journal of Cardiovascular Electrophysiology 2003;14:705-711.

8. Kop WJ, Krantz DS, Nearing BD, Gottdiener JS, Quigley JF, O’Callahan M, Delnegro AA, Friehling TD, Karasik P, Suchday S, Levine J, Verrier RL. Effects of acute mental and exercise stress on T-wave alternans in patients with implantable cardioverter defibrillators and controls. Circulation 2004;109:1864-1869.

9. Shusterman V, Goldberg A. Upsurge in T-wave alternans and complex-form repolarization instability precedes the onset of spontaneous ventricular tachyarrhythmias in humans [abstract]. Circulation 2004;110;III-667.

10. Nearing BD, Verrier RL. Progressive increases in complexity of T-wave oscillations herald ischemia-induced VF. Circulation Research 2002;91:727-732.

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My understanding is that other methods of measuring TWA exist that do not require expensive electrodes. The cost implications are substantial.

The literature supporting T-wave alternans to date are based on small studies of biased samples (e.g. mainly patients referred for EPS studies). No published RCTs have shown that TWA improve outcome.

Pending the results of very large observational studies based on less biased samples and properly performed RCTs, TWA, in my opinion, is not yet ready for routine clinical use. Furthermore, by requiring that only one company's method be used, the costs to be born by American taxpayers will be substantial.

Many thanks for your consideration.

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I am a Electrophysiologist inmetro DetroitI implant more than 250 ICD's per year and though I have a obvious monetary insentive to expansion of ICD implant coverage , In my opinion is is wasteful to apply ScHeft criteria to all patients we see in our daily practice so I welcome the strong scientific evidence avilable to us that strongly suggest TWA testing as a inexpensive screening test to better choose true patients at risk when properly used this test will reduce the number of unnecesary implants by 50%(NNT would go from 14 to 7 if we apply data from JACC VOl 47 Jan 17th 2006 Bloomfield et al)

We have our own research on TWA results and cardovascular outcome with very similar results as far as good outcome correlating with negative TWA

This nation can not afford wasteful utilization of ICD's, not all aptients who are candidates to ICD for primary prevention need one, being a candidate does not make you a winner, it means thoghtful process of risk/benefit evaluation must be applied and with TWA this process is simple, better and probably more cost effective

The data is available: Hohnloser SH, et al. JACC 2003, Kitamura H JACC 2002,Grimm W et al Circualtion 2003Lets make it possible for physisan to be reimbursed for the cost of TWA testing, they will make the differnce not the ICD's companies, not ambrige Heart, not the FDA

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The following are my thoughts and opinions, which are offered to address your request for comment on the pending decision to utilize T-wave alternans (TWA) in sudden death risk stratification in Medicare and Medicaid patients. I have had a longstanding interest in this phenomenon. More than 30 years ago, I published an article. “Electrical alternation of the T- wave: Clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome” in the American Heart Journal (1975, volume 89, pages 45-50). I believed then as I do now that TWA is a fundamental marker of risk for arrhythmias, which is important not only in patients with the long QT syndrome but more broadly in terms of patients with myocardial ischemia and infarction, heart failure, and other conditions. It has been highly significant that sophisticated analytical methods have been developed over the last decade to quantify the magnitude of TWA in order to predict arrhythmic events. Thus, I support CMS’ decision to provide reimbursement for TWA testing.

However, I do not believe that it is justified or appropriate to restrict the analytical technique to the spectral method. In fact, I have personal experience with the Modified Moving Average approach as the senior author of a multicenter investigation in post-myocardial infarction patients, the ATRAMI study, in which TWA predicted arrhythmic death or cardiac arrest during the two-year followup. This peer-reviewed study was published in the highly regarded Journal of Cardiovascular Electrophysiology (2003;14:705-711), which has a strong impact rating. The patients under study were at relatively low risk of lethal arrhythmias and therefore constitute a major cohort of risk in the Western world, including the United States. Although TWA analysis was performed on archived recordings, it was executed according to a priori hypotheses by an investigator who was blinded regarding clinical outcome. Therefore the study qualifies as prospective not retrospective. Importantly, TWA was found to provide predictive information in addition to left ventricular ejection fraction. This important study was not cited in your proposed decision memorandum although it fulfilled your criteria for literature review.

The Modified Moving Average method has the advantage of not requiring specialized electrodes or a nonstandard exercise protocol and can be implemented not only in routine treadmill testing but also in ambulatory ECG monitoring. I know that the method has been evaluated in expert engineering studies and found to be sound. In another peer-reviewed paper, TWA was employed to evaluate electrical instability in patients with ICDs (Kop et al in Circulation 2004;109:1864- 1869).

In summary, I believe that it would be unwise to restrict clinical evaluation of TWA to a single method, when there is a completely valid alternative method with distinct advantages including cost savings is available.

Sincerely,

Peter J. Schwartz, MD
Professor & Chairman
Department of Cardiology
Policlinico S. Matteo IRCCS
Viale Golgi, 19
27100 Pavia, Italy

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I AM A TECH THAT PERSONALLY SUPERVISED 67 T-WAVE ANALYSES AND CAN ATTEST TO THEIR EFFICACY AS WELL AS THEIR EASE OF ADMINISTERING. THE PATIENTS ARE RELIEVED THAT THERE ARE NO INJECTIONS, ONLY 14 ELECTRODES AND THAT THE TREADMILL PORTION IS A LOW LEVEL PROTOCOL. IT IS A FAST AND EASY TEST WITH INSTANT INTERPRETIVE VALUE. THE RESULTS OF THE TEST ARE EASILY INTERPRETED, THERE ARE ONLY THREE OPTIONS: POSITIVE, NEGATIVE AND INDETERMINATE AND INDETERMINATE CAN BE RECTIFIED WITH AN IMMEDIATE FOLLOW UP TEST IN MOST SITUATIONS. ALL 17 OF OUR POSITIVE TESTS HAVE BEEN REFERRED TO ELECTROPHYSIOLOGY FOR EP STUDY AND 16 HAVE RECEIVED DEFIBRILLATORS. THE 17TH HAS YET TO BE SEEN BY EP. BUT PERSONALLY I THINK THE GREATEST ACCOMPLISHMENT OF THE T-WAVE TEST HAS TO BE HOW EASY IT IS FOR THE PATIENT TO ENDURE, AS WELL AS THE COST COMPARED TO EP EVALUATION. THANK YOU.

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This comment is submitted in support of the Proposed National Coverage Determination for Microvolt T-Wave Alternans (MTWA). Cambridge Heart is pleased that CMS has recognized the importance of Microvolt T-Wave Alternans concluding that there is sufficient evidence to determine that the use of Microvolt T-Wave Alternans is reasonable and necessary for the evaluation of Medicare beneficiaries at risk for sudden cardiac death (SCD). The decision memorandum correctly recognizes that MTWA diagnostic testing is only reasonable and necessary if measured employing the analytic spectral method as clinically validated in the peer reviewed medical literature. This decision will have a significant impact on improving the quality of the care of Medicare beneficiaries.

The proposed decision memorandum notes that 1028 citations were submitted in support of the NCD. Additionally, CMS reviewed and relied on 12 of the submitted peer reviewed clinical articles for its determination that coverage of MTWA is reasonable and necessary. I would like to bring to CMS’ attention that since the completion of your literature review four additional papers have been published in the cardiology peer reviewed literature. These newly available articles each strongly support all elements of the proposed decision memorandum.

This comment letter briefly summarizes these articles which have been submitted to CMS for inclusion in the public record via separate email.

1) Journal of The American College of Cardiology

On December 5, 2005 the Journal of The American College of Cardiology published, online under expedited review, for print publication in their January 17, 2006 edition “Microvolt T-Wave Alternans and the Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction.” This study of 549 Heart Failure patients with an ejection fraction < 40%, funded by grants from the National Heart, Lung and Blood Institute of the NIH, the Doris Duke Charitable Foundation and Cambridge Heart, demonstrated the benefit of utilizing MTWA to assess patients similar to those evaluated in the SCD-HeFT Trial. The conclusion of the study, whose Principal Investigator was Dr. Daniel Bloomfield, is “Amongst patients with heart disease and LVEF < 40%, MTWA can identify not only a high risk group, but also a low risk group unlikely to benefit from ICD prophylaxis.” It should be noted that this study was performed utilizing the Analytic Spectral Method.

2) International Journal of Cardiology

The International Journal of Cardiology published a study in 2005 by Dr. Massimo Baravelli that looked at NYHA Class II Heart Failure patients and prospectively studied patients with an EF<45% utilizing bicycle as the method of exercise. With end points of SCD, documented sustained VT/VF and appropriate ICD shock no events occurred in the MTWA negative patients, which numbered 36% of the 73 Class II patients studied. Again the method used was the Analytic Spectral Method.

3) Nature Clinical Practice Cardiovascular Medicine

Armoundas, Hohnloser, et al, published an interesting Meta Analysis in the October, 2005 issue of Nature Clinical Practice Cardiovascular Medicine. In this analysis four prospective, peer reviewed publications were combined for their similarity to what has been called the primary prevention group of patients. Across the entire 851 patients in the four studies the annual all cause mortality rate for MTWA normal / negative patients was 2.0% as compared to an annual all cause mortality rate of 7.4% in the ICD patients in a blend of the 3,753 patients enrolled in the MADIT II and SCD-HeFT studies. Their conclusion indicated that this large body of data indicates that primary prevention ICD candidates should undergo MTWA testing and that the test in consultation with the patient’s physician could help define appropriate therapy. Again, all of these studies utilized the Analytic Spectral Method.

4) Journal of the American College of Cardiology

A “State of the Art” paper appears in the January 17th issue of Journal of the American College of Cardiology, entitled, “T-Wave Alternans and the Susceptibility to Ventricular Arrhythmias.” Dr Sanjiv Narayan looks at the MTWA technology examining both the bench data as well as the clinical literature. In the abstract Dr Narayan states, “Collectively, these studies provide a foundation for clinical use of MTWA to reflect susceptibility to ventricular arrhythmias in several disease states.” He discusses incorporating TWA into clinical risk stratification algorithms.

These four recently published articles provide further documentation and support for the CMS proposed decision. By way of a small technical correction for the final decision memorandum, the method of analysis is more correctly referred to as the “Analytic Spectral Method.”

I look forward to the conclusion of the NCD process and have appreciated the time and attention of CMS to this issue. The openness of the process is quite helpful in getting useful information into discussion in an efficient manner.

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I am writing in response to the solicitation for public comments following release of your draft decision regarding the National Coverage Analysis on the use Microvolt T-wave Alternans testing (CAG-00293N) for the evaluation of patients at risk for sudden cardiac death. I am a clinical electrophysiologist and clinical researcher affiliated with New England’s major Veteran Administration EP program, Beth Israel Deaconess Medical Center, and Harvard Medical School.

I agree fully with and strongly support the decision presented in the draft memo, and the analysis underlying it. Microvolt T-wave alternans performed using the spectral analytic method now has a sufficient body of clinical evidence from well-conducted studies to support its use as a risk-stratification tool in the proposed populations. As stated in the draft decision, reimbursement approval of MTWA by CMS does not and should not mean that this testing is required prior to ICD implantation in populations eligible for ICDs under current guidelines. It only means that Medicare will pay for the test if doctors and patients want to use the information the test provides as an aid in clinical decision making.

In the current issue of the Journal of the American College of Cardiology, more data were published from a prospective multi-center, NIH- funded study on this topic. In the ~550 patients studied, MTWA again proved its predictive accuracy to be additive and superior to a variety of demographic, health history and non- invasive markers used to assess the risk of sudden death, including ejection fraction, QRS duration, and heart failure severity. The data in this report are highly consistent with that reviewed in the draft memo, and support the utility of MTWA not only for patients with ischemic heart disease, but also for patients with non-ischemic cardiomyopathy, in whom few risk markers previously shown promise.

Patients with abnormal MTWA tests are 4-6 times more likely to experience life-threatening ventricular arrhythmias than patients with normal MTWA tests. This information can be used to promote appropriate referral of patients identified to be at truly high risk for sudden death for prophylactic ICDs. A negative test result has also been shown to have a very high (>95%) negative predictive value. This identifies a population with a low probability of receiving short-term benefit from ICD implantation, information that may be helpful in cases where patients or their physicians have doubts about the potential benefit of an ICD. Such doubts have recently increased in frequency in the wake of a number of ICD product recalls.

It is worth noting that the specific language of the draft memo regarding the method used to analyze MTWA – the spectral analytic method – is supported by the clinical literature. The prognostic significance of t-wave alternans identified using other techniques has not been established in large-scale clinical studies.

The preliminary decision you have released is entirely appropriate. I urge you to finalize it without change, aside from perhaps incorporating the new data published this week into the decision memo.

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I strongly support the CMS decision on payment for micro T wave alternans testing. This test can substantially improve clinical decisions on ICD placement. There is now substantial documentation that a negative micro T wave alternans test predicts a very low risk of cardiac arrest in patients who otherwise meet the usual criteria for ICD placement for primary prevention suggesting that these patients should not have ICD placement. On the other hand, a non-negative test substantially increases the PPA for an arrhythmic event in those patients who meet the ejection fraction and clinical class criteria. This information could be extremely useful in those patients who had ICDs placed for primary prevention and who have not had appropriate shocks and have either recalled units or end of life units. Furthermore, separating the low ejection group into those likely to die of arrhythmias versus those more likely to die of heart failure should lead to more rational therapy. Sincerely, Robert E. Kleiger, M.D., F.A.C.C. Professor of Medicine

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I have had MICROVOLT T-Wave Alternans testing in the office for about three years. I find it very, very helpful in decision making regarding AICD implants. We have not had a sudden cardiac death in a negative T-Wave Alternans patient in our practice here at Regional Cardiology Consultants.

I think the technology should be used to a much wider extent. It is most helpful in a patient with limited lifespan and decision making regarding AICD and for decisions regarding arrythmic therapy.

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I am a member of a large group practice in cardiology and the medical director for non-invasive services at Aspirus Wausau Hospital and The Wausau Heart Institute. For roughly 2 years my partners and I have used the Cambridge Heart MTWA system as a risk stratification tool for patients potentially at risk for sudden cardiac death from malignant ventricular arrythmias. After a careful review of available literature we were reasonably confident that the results of the MTWA test could be used as a method of identifying patients who could be treated without the use of an automatic implantable defibrillator that might otherwise be indicated by other clinical findings (i.e low ejection fraction). Thus far it is our impression that a normal MTWA test indeed identifies a subgroup of patients at sufficiently low risk to support the clinical decision not to implant a device. We anticipate this test will continue to be useful in a wider cohort of patients including those with unexplained syncope and hypertrophic cardiomyopathy. We strongly support the recent CMS proposal to expand Medicare beneficiary access to microvolt t-wave alternans testing.

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I came to know of MTWA only recently, and what I found astounded me...For years the ability to predetermine, with a reasonable degree of error, the chances of sudden cardiac death..and not only in the positive but to exclude as well...Yet, as we sit here today, 9 yrs since Mr. Cohen working with NASA discovered the predictive value of MTWA, we are still discussing the reasonableness and necessaryness of MTWA..Why?...Guidant, Medtronic, St. jude, J J,,,,Yes, their products save lives, and are critical to our nations healthcare system,..However, they have been taken in by Wall street, in a thirst for growth, and have continuely stymied MTWA from gaining access to doctors offices...Isnt it so obviuos,,,Read posts from respected doctors around the world speak from the heart regarding the immediate need to move forward...With the broadening pie of available patients, icd growth, with MTWA leading the way, will continue to expand...Prescreening of patients , will benefit everyone involved...The healthcare system will save millions of dollars in many different ways, icd growth will expand and with even greater confidence, doctors will increase revenue sources, and patients most importantly will be spared the indignity, of having an unnecessary device, implanted, for no reason what so ever...I offer my statements , not as opinion, but as factual, and I offer this article written by two asteemed doctors who have posted here today...When i read their comments, I knew they had bias, and for some reason they were collaborating in their ongoing attempt to scuttle MTWA...Today they wrote one thing, but 2 years ago, you both felt differently...Thank you ...http://circ.ahajournals.org/cgi/content/fu ll/108/15/1779

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I applaud the CMS proposal to expand the indications for MTWA testing using the Analytic Spectral Method.

MTWA provides me with a noninvasive diagnostic tool that allows me to assess my patients' risk of sudden cardiac death. This will ensure that the most appropriate primary prevention patients will be referred out for ICD therapy. In addition the negative predictive value has held up across all of the clinical data.

Please approve asap. Thank you for allowing me to comment.

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I am responding to your invitation to provide public comment regarding the pending decision to utilize T-wave alternans (TWA) in sudden death risk stratification in Medicare and Medicaid patients. This is a topic with which I am highly familiar, as Co-Director of the Coronary Care Unit and Director of the Ambulatory ECG Research Laboratory at the Brigham &Women’s Hospital in Boston, which is a teaching hospital of Harvard Medical School.

While I support the decision that TWA is a useful noninvasive marker of arrhythmia risk, I believe that the test should not be limited to the spectral analytic method. Our group has had experience with the Modified Moving Average method of TWA analysis in patients with stable ischemic heart disease who are enrolled in the NIH-supported “Vascular Basis for Treatment of Myocardial Ischemia Study” (Stone et al 2005, Nearing et al 2004, listed below). Not only has the Modified Moving Average method proven to be highly accurate but it also has distinct advantages over the spectral method, as it can be performed using standard electrodes during a routine exercise treadmill test. The full disclosure features are extremely helpful, allowing multiple clinical indicators to be compared along with TWA, namely, ST-segment changes, arrhythmia, and heart rate recovery patterns.

Thus, I believe that TWA is a useful clinical parameter but that limiting reimbursement to the spectral method is inappropriate and would deprive patients and their physicians of an alternative test, which can be performed in a cost-effective and efficient manner during the stream of clinical evaluation.

Nearing BD, Stone PH, Verrier RL. T-wave alternans is associated with spatial heterogeneity of T- wave morphology in CAD patients during treadmill exercise. J Am Coll Cardiol 2004;43:168A.

Stone PH, Lloyd-Jones DM, Kinlay S, Frei B, Carlson W, Rubenstein J, Andrews TC, Johnstone M, Sopko G, Cole H, Orav J, Selwyn AP, Creager MA. Effect of intensive lipid lowering, with or without antioxidant vitamins, compared with moderate lipid lowering on myocardial ischemia in patients with stable coronary artery disease: the Vascular Basis for the Treatment of Myocardial Ischemia Study. Circulation 2005;111:1747-55.

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I am writing to respond to the solicitation of public comment regarding the recent proposed decision for CMS coverage for T-wave alternans (TWA) testing for noninvasive sudden cardiac death risk stratification. My views derive from decades of experience in caring for patients at risk for arrhythmic death using both invasive and noninvasive techniques. I have personally evaluated many TWA tests using the Cambridge Heart system at our medical center, which is a teaching hospital of Harvard Medical School.

It is my view that reimbursement for TWA testing should not be restricted to the spectral analytic method, as there is a valid additional approach, the Modified Moving Average method, which has distinct advantages, as discussed below. The restriction in the proposed decision memorandum is apparently based on insufficient knowledge of the testing and results of the Modified Moving Average algorithms, as evidenced in the statement in the CMS document http://www.cms.hhs.gov/mcd/viewdraftdecisionmemo.asp?id=165 on page 14, section VIII, final sentence: “There are other methods which can be used to measure MTWA (e.g., modified moving average), though we found no peer-reviewed published articles discussing these algorithms at the time of our analysis. Currently, the evidence only supports the use of spectral analysis algorithm for the detection of MTWA.”

Drs. Verrier and Nearing at our institution have published engineering validation of performance characteristics of Modified Moving Average analysis and experimental study evidence of the accuracy of T-wave alternans as analyzed by this method in predicting ischemia-induced ventricular fibrillation. Their peer-reviewed study, “Modified moving average method for T-wave alternans analysis with high accuracy to predict ventricular fibrillation,” appeared in Journal of Applied Physiology in 2002 (volume 92, pages 541- 549). The Modified Moving Average technique has also been independently tested and evaluated by Martinez and Olmos and found to be superior to the spectral method, as reported in their peer- reviewed article, "Methodological Principles of TWave Alternans Analysis: A Unified Framework," published in IEEE Transactions on Biomedical Engineering in 2005 (volume 52, pages 559-613). This exhaustive and scholarly review of existing methods for TWA analysis concludes, “...two recently proposed methods (Modified Moving Average and Laplacian Likelihood Ratio Method) form at the moment the category of nonlinear filtering methods. These are intrinsically robust to outliers or impulsive noise and have shown to perform better than linear methods in physiological noise.”

Importantly, the FDA has cleared the use of the Modified Moving Average method of TWA analysis for sudden death risk stratification at 1- microvolt resolution. The FDA clearance document (K032513) for GE Medical System’s “ECG analysis algorithm” commented, “The TWA Algorithm measurements have been found to be predictive of arrhythmic death and can be used for the purposes of risk stratification.” Also, the American Medical Association does not restrict its “Current procedural terminology” (CPT) code 93025 for “Microvolt T-wave alternans for assessment of ventricular arrhythmias” to the spectral method.

Furthermore, peer-reviewed clinical data demonstrate the capacity of the Modified Moving Average approach to detect cardiac electrical instability in patients with implantable cardioverter defibrillators (ICDs). Kop and coworkers recently published a peer-reviewed study in the leading cardiology journal Circulation (2004; volume 109, pages 1864-1869), which demonstrated that patients with ICDs exhibit significantly higher levels of TWA during mental stress as well as during initial and peak levels of exercise as compared with age-matched healthy volunteers.

The Modified Moving Average method for TWA analysis, which is incorporated into GE Healthcare’s standard exercise stress test equipment, has several important cost-saving and efficiency-of-use advantages over the spectral analytic method. The Modified Moving Average method works with standard protocols and electrodes and thus circumvents the need for separate equipment, for performing an additional protocol, and for the costly proprietary Cambridge Heart electrodes, which are sometimes painful to remove. With GE’s exercise stress test system, ease of use and efficiency are increased, further decreasing costs, as TWA values are reported along with all of the standard data, including full disclosure of ST- segment changes, heart rate recovery, arrhythmias, etc.

Thus, based on extensive peer-reviewed methodologic assessment, FDA regulatory approval, and emerging clinical evidence, as well as efficiency, I believe that it is not appropriate to exclude Modified Moving Average analysis from CMS coverage. Specifically, I recommend deletion of the words “only when the spectral analytic method is used” from the National Coverage Determination. The second sentence of the proposed decision (“We are also proposing that MTWA diagnostic testing is only reasonable and necessary if measured employing the spectral analytic method”) should also be removed.

Sincerely,

Mark E. Josephson, M.D.

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MTWA testing removes the barrier to entry to insure the most appropriate primary preventions patients are referred to the implanting specialists.The positive predictive value of MTWA helps identify those patients most likely to benefit from ICD therapy.MTWA testing is a clinical proven risk stratifier that enables me to openly discuss a patient's level of risk and need for an ICD.Implanting every primary prevention ICD eligible patients is not a cost effective use of our valuable health care resources. Since we know that only 20% of ICDs fired appropriately in the SCD-HEFT trial, the use of MTWA testing can help differentiate those patients at highest risk from those that might be best managed medically.

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MTWA testing is important and help to insure most apppropriate primary preventionspts are referrd to implanting doctorit also has negative prdictive valuepositive prdeictive vlaue help pats most likerly benefit from ICDmtwa testing is a clinical proven rikd stratifier and help me discusee with my patients level of ridk and need for icdsince we know oly 20 % icd fired appropriately in trials use of mtwa testing will help differentiate those patients at highest riskplease contact if any questions

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I am a cardiologist in private practice. We have a group of four cardiologists,none of whom are electrophysiologists. A very common problem in our practiceis the appropriate referral for implantation of implantable defibrillators. This concern is not small, as you know, with risk both ways; i.e., if we referpeople who are not candidates, they may end up with a defibrillator they don'tneed, thus facing the risk and the expense of the procedure. On the otherhand, if we don't refer patients who are in need of the defibrillator, suddendeath may be the next outcome.

Clearly in this setting, a noninvasive, easily done, reliable risk stratifier totell us which group of patients does not need implantable defibrillators wouldbe of great value.

I believe that the multiple studies supporting microvolt T-wave alternans (MTWA)as performed by the Cambridge Heart technology supplies this need. Nearly allstudies of MTWA have shown extremely low event rates in MTWA-negative patients.

Although I know that financial considerations cannot be first in line in these decisions, they are still nonetheless important because of the huge financialimpact of putting defibrillators in everybody with an ejection fraction below 35%.

In our practice, we find only one out of three people who meet current criteriaas established by the MADIT II trial actually are positive when tested withMTWA. We test approximately six patients per week. Assuming a cost of $400per MTWA and a cost of $50,000 per implantable defibrillator, a rough estimateis something in the range of $5 million saved per year in avoiding implantabledefibrillators that are not indicated in our practice alone. This obviouslydoes not take into consideration the added trauma and risk to patients ofgetting implantable defibrillators that are not indicated.

At this point in time, MTWA is the only risk stratifier that has this proventrack record and I strongly encourage you to consider including the use of thistechnology in risk stratification of patients with left ventricular dysfunctionfor consideration of implantable defibrillators.

Sincerely,
C. David Akin, M.D., F.A.C.C.
Independence Cardiology Associates, PC
1515 West Truman Road, Suite 602
Independence, Missouri 64050

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I would like to comment on CMS' draft decision on Microvolt T-wave Alternans testing. I am in strong agreement with CMS to utilize MTWA testing (from Cambridge Heart) to determine which patients are at risk for sudden cardiac death.

As an internist it is extremely important to me to be able to utilize MTWA testing in my practice. MTWA allows me to rule patients out for SCD with its high negative predictive value and identify the high risk patients who test positive. This way only the patients in absolute need of an ICD are referred out. I support the NCD for MTWA. Thank you.

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Re: The Microvolt T-wave Alternans Test (from Cambridge Heart) used to determine which patient requires an ICD

I would like to express my strong agreement with CMS to utilize the Microvolt T wave Alternans Test (from Cambridge Heart) to determine which patients are at risk for sudden cardiac death. The high negative predictive value of this test will ensure that only those patients in absolute need of an ICD will receive one. What with the inherent problems of ICDs (not to mention expense), this relatively simple test is long overdue.

Thank you,
Kathleen Fuchs, M.D.

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I applaud the CMS proposal to widen the scope of reimbursement for the T-wave alternans test.

TWA testing has been shown to substantially improve risk stratification for sudden cardiac arrest over existing methods. However, it has yet to be incorporated into Professional clinical pathways or guidelines for this purpose. Broadening the reimbursement for TWA testing removes a potential obstacle for wider use of this tool in prospective or registry studies. In turn, such studies should identify populations for whom TWA testing should ideally be incorporated into clinical guidelines for risk stratification.

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Please review and accept my comment on the upcoming decision by CMS related to national coverage for Microvolt T-wave Alternans testing.

It would seem to be a contradiction For CMS to currently provide national coverage for ICD therapy (costing tens of thousands of dollars) in patients who are candidates for primary prevention ICD therapy and to not provide national coverage for a test (well under a thousand dollars). The MTWA test has been shown in studies and commented on by various organizations and companies to potentially be a valuable tool when considering having ICD therapy or maybe more importantly, a tool to be used in the choice to not have the now controversial, expensive and flawed ICD therapy. It is now public knowledge that the current testing processes may not be adequate enough to satisfactorily draw the conclusion as to have the ICD therapy or not. A small percentage of the devices are flawed but yet millions of dollars were spent to implant them! With the recent and well-publicized ICD news, ICD recalls ...etc. , The use of MTWA testing should not only be a candidate for national coverage but should also be a mandatory part of the ICD therapy process if at all possible due to testing unit availability. CMS is already covering the very expensive ICD therapy. Why not include mandatory MTWA testing along with it so that data could be collected nationally from the test on an ongoing basis. By making the MTWA testing a mandatory part of the ICD therapy process, the testing data could then be collected and then analyzed for future CMS decisions on related coverage issues. At the very least have the MTWA testing done after the decision to go ahead with the ICD has been made for the purpose of collecting data. The decision to have the ICD therapy (or not) does not have to be based on the MTWA testing results alone. It has been suggested that further evidence be collected before national coverage by CMS be allowed. The test itself is non-invasive, relatively inexpensive as compared to an ICD and can be done in a doctor’s office. It is the MTWA testing data collection that is of utmost importance now and a decision to have the MTWA mandated and covered nationally would likely have the potential to provide for a more efficient use of healthcare funds and to improve upon our nations healthcare and support its technological advance in non-invasive testing procedures. Waiting for further studies to be made on a cheap non-invasive test wouldn’t seem to be the best course to take considering the potential usefulness of the test.

Thanks,

Mike Bull

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There is compelling evidence that the MTWA test is a powerful predictor of sudden cardiac death risk. Its value lies not only in its positive, but perhaps more importantly, its negative predictive accuracy. The results of the recently NIH-sponsored trial of Bloomfield and coworkers are so strong that the proposed NCD is clearly justified. I believe, however, that a word of caution is in order. While there is little doubt about the ability of the MTWA test to identify a low-risk cohort, it is not at all clear how long into the future that prediction remains valid. Indeed, the MTWA- patients who experienced events (e.g. four individuals in the above mentioned study) could conceivably have changed their MTWA status after the index recording and thus not be true false-negatives. Until future studies can address this important question, I believe that MTWA- patients who would otherwise be considered candidates for ICD implant should undergo periodic testing to reconfirm their MTWA- status. In light of published data MTWA repeat testing every 1-2 years may be a reasonable choice.

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The cardiology community is grateful for the broad coverage decision for ICD prophylaxis (primary prevention) rendered by CMS in January 2005. Similarly, cardiologists will be grateful for coverage for microvolt T-wave alternans (MTWA) testing, which will permit better selection of patients for ICD prophylaxis. CMS is not proposing mandatory use of MTWA for selecting patients for ICD nor is it suggesting that the results of a MTWA should mandate a particular action. MTWA results are to be used along with other pieces of information to inform complex decisions about when to use of ICD for primary prevention (prophylaxis). There are very few, if any, mandated uses of ICD prophylaxis; each implant decision should be preceded by a thoughtful benefit/risk evaluation. If a physician wants the results of a MTWA test to help with a decision for an individual patient, the test should be available and reimbursed.Cardiologists recognize that the absolute benefits of ICD prophylaxis found in MADIT II or SCD HeFT were relatively small and that 14-18 ICD must be implanted to save a life. About 80% of ICD implanted prophylactically never provide therapy, a finding that is motivating the search for better selection of appropriate patients for this potent therapy.A strategy used by our group and others is to search among patients eligible for ICD prophylaxis under current guidelines to find those who are unlikely to ever have a sustained ventricular tachyarrhythmia and are therefore unlikely to benefit from ICD implantation. Steadily accruing evidence indicates that MTWA by the spectral method is one of the best tests available today for this purpose by virtue of its high negative predictive accuracy (low false negative rate) in patients who are eligible for implants by MADIT II or SCD HeFT criteria. MTWA tests are normal (negative) in about 35% of these patients. Arrhythmic events (sudden death, resuscitated cardiac arrest, or sustained ventricular tachycardia) are rare in patients with normal MTWA tests (1-2% per year). Thus, MTWA tests increase positive predictive accuracy modestly and militate against ICD implants in about 1/3 of candidates. Those excluded from ICD prophylaxis by a negative MTWA test have very little risk of an arrhythmic event and very little chance of deriving benefit from ICD prophylaxis.

The benefit to patients with normal MTWA tests is obvious. But, there are benefits to patients who have abnormal MTWA tests as well. At present, it is estimated that only about 10% of the patients with a MADIT II or SCD HeFT indication for ICD prophylaxis avail themselves of the opportunity to have an ICD implanted prophylactically. The causes for such poor penetration of a proven therapy lie with physician or patient acceptance. Many patients confronted with the prospect of ICD prophylaxis wonder why the issue is coming up after months or years of seeing a doctor for a stable cardiovascular condition. When abnormal, MTWA should encourage better compliance with practice guidelines to the benefit of patients treated prophylactically with ICD therapy.

MTWA also should play an important role in informing discussions between doctors and patients revolving around the currently active ICD recalls and advisories. MTWA can identify patients who are unlikely to develop ventricular tachyarrhythmias, a factor that looms large in the list of factors to consider in making the decision about whether or not to replace an ICD that is subject to recall.

Just as CMS has been scientific and generous in covering ICD prophylaxis, it has made a studied judgment that it should provide coverage for MTWA and thus provide internists and cardiologists a vital tool for deciding which patients should be treated prophylactically with an ICD and to help with difficult decisions about which ICD to replace during a recall.

MTWA has the following favorable features:

I am an Internal Medicine physician and have been using MTWA testing in my practice. MTWA has been extremely helpful in assessing my patients' risk of sudden cardiac death. MTWA gives me an inexpensive, non-invasive diagnostic tool to indentify low and high risk patients.

The clinical data clearly supports its use in patients with cardiomyopathy, as well as, syncope, post MI etc. The negative predicative value has held up in all of the clinical studies. This gives me confidence and piece of mind that I can manage the negative MTWA patient more conservatively. In addition, if a patient tests MTWA positive I can refer that patient out for the appropriate therapy.

I support the NCD proposal for MTWA.

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Over last several years, there were several studies conducted indicating predictive value of T wave alternans testing. Importantly, negative predictive value is very high (above 90%) - indicating clinical usefulness of TWA for identifying patients at low risk of arrhythmic events at teh time of testing. Performing TWA testing in high-risk patients might help prioritizing patients for ICD therapy. Those with negative test could have ICD postponned and TWA test repeated either on periodic (yearly) basis or after additional clinical event (including acute myocardial ischemia). Patient is a moving target, meaning that myocardium over time might become arrhythmogenic and TWA might help identifying proper timing for ICD therapy. Simultaneously, patients with low risk of arrhythmic events might avoid preamture treatement with ICDs. Such triage could help in clinical decision process as well as it could bring down the costs of the ICD therapy in vulnerable population. In addition to patients with current ICD indications, TWA seems to be useful in identifying patients at risk of arrhythmic events who are not covered by current ICD indications. In such patients, who are particularly difficult to risk stratify, TWA might work as useful test identifying high-risk subsets. Prospective studies are needed to document the usefulness of TWA for identifying high-risk individuals aming patients not covered by current ICD guidlines.

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