Ventricular Assist Devices as Destination Therapy

I would like to thank the CMS team for continuing to evaluate coverage for new therapies and technologies improving care options for your beneficiaries. As a cardiothoracic surgeon at an academic center, I have seen the benefits of both permanent and heart recovery LVAD therapies for my patients. The studies referenced by Dr. Slaughter, Dr. Frazier and colleagues demonstrate the improvements in the Heartmate II LVAD. The coverage decision should be expanded as recommended to include all chronic NYHA class IV heart failure patients. I would also recommend changing the reference to balloon pump to be more consistent with clinical practice for hemodynamic support. Although the intra-aortic balloon was included in this study and a common therapy for heart failure patients, surgeons incorporate several short term devices in daily practice including FDA approved or cleared devices such as cardiopulmonary support, recovery LVADS, and others. These may be more beneficial for class IV patients as a balloon pump ironically is not a pump at all, it simply changes pressures in the aorta. ACC/AHA guidelines and publications support the use of these devices for class IV patients including Mark Anderson, MD et al, Ann Thorac Surgery 2010;90:706-12. This is the largest known study of LVADs in Cardiogenic Shock and it documented outcomes for heart recovery and support prior to permanent LVAD placement. The study also references heart recovery as the most likely outcome for survivors. The coverage language states permanent LVADs are for chronic heart failure only, however I would recommend CMS confirm AMI shock and acute heart failure is not the intended or studied population. Sincerely, Dr. Mark Anderson

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Abiomed supports the general recommendations for updating the coverage language and requirements for permanent LVAD technologies. We concur with the conclusions of the CMS coverage team in general, however request clarification be incorporated into the final language in relation to “balloon pump for 7 days” and “chronic end-stage heart failure”.

Additional language adding intra-aortic balloon patients: “ …or a patient is balloon pump dependent for 7 days…”The study by Dr. Mark Slaughter (Slaughter MS et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241-51) provides data on balloon pump support with both Heartmate XVE and Heartmate II LVAD technologies. The recommended coverage language refers to a specific type of device used for hemodynamic support (balloon pump), however there are many different hemodynamic support options in general clinical practice with similar FDA labeling. This includes cardiopulmonary support systems, centrifugal pumps, short term LVADs, extracorporeal membrane oxygenation, and circulatory support systems. Use of a specific device in the coverage language could alter clinical practice for short term support prior to permanent LVAD. The publication by Dr. Mark Anderson (Use of the AB5000 ventricular assist device in cardiogenic shock after acute myocardial infarction Anderson M, Smedira N, Samuels L, Madani M, Naka Y, Acker M, Hout M, Benali K. Ann Thorac Surg. 2010 Sep;90(3):706-12.) also provides outcomes data on recovery LVADs including a subset supported to transplant or Heartmate LVAD. Abiomed recommends this language be consistent with ACC/AHA guidelines using a more general term “hemodynamic support for 7 days” (Smith et al, Circulation 2001;103;3019-3041) or be removed as survival outcomes for this subset are not provided in the referenced publication.

Clarification on chronic heart failure intended use: “The VADs are covered for patients who have chronic end-stage heart failure (New York Heart Association Class IV end-stage left ventricular failure), who are not candidates for heart transplantation, and meet all of the following conditions:…”

The language provided in the coverage document states “The VADs are covered for patients who have chronic end-stage heart failure (New York Heart Association Class IV end-stage left ventricular failure), who are not candidates for heart transplantation, and meet all of the following conditions.” This patient population is in need of alternative therapies and Abiomed supports this recommendation. We are concerned, however, that the current language in Appendix A may allow for patients that would include acute heart failure (i.e. acute myocardial infarction, viral myocarditis) that are commonly treated by other technologies such as the AB5000 which is approved by the FDA for these recoverable indications. Case example: a Medicare beneficiary with no prior history of chronic heart failure experiences a heart attack or viral attack. This patient would be diagnosed on days 1-7 of balloon pump therapy and ICU care as a Class IV heart failure patient, , and transitioned to a destination therapy device without an attempt to recover the heart muscle with FDA approved devices. We believe this is not the intended population for the coverage language as provided and request confirmation. With the proposed removal of device FDA labeling requirements and 90 day prior history of heart failure in the proposal, CMS may inadvertently be supporting the use of the Heartmate XVE and Hearmate II devices for a recovery indication prior to any clinical studies or FDA approvals for this indication.

The study (referenced above) published in the Annals of Thoracic Surgery in September 2010 documents the outcomes of 100 AMI patients treated with an LVAD approved by the FDA for recoverable indications. The authors noted that 91% of the cardiogenic shock patients who recovered from the acute event were on balloon pump therapy and the most likely outcome of survivors was native heart recovery. The authors also noted the LVAD was used successfully as a bridge to transplant or permanent LVAD in 15% of the patients. Although this is a much sicker patient population than generally treated by permanent LVADs, it demonstrates the use of FDA PMA approved devices for short term support. The need to allow time for heart recovery prior to transplant or permanent LVAD technology was also raised by the authors.

Recommendation: The coverage language proposal removes the requirement for documented chronic heart failure (90 days), use according to FDA labeling, and inserts a patient on balloon pump for 7 days. We recommend adding a statement that clarifies “excludes treatment of acute heart failure patients with no prior history of chronic heart failure”. Alternatives are to keep the original coverage language of chronic heart failure “for at least 90 days” or add “for patients who have a history of chronic end-stage heart failure (New York Heart Association Class IV end-stage left ventricular failure)” with detailed guidance to fiscal intermediaries about acute heart failure.

Andrew Greenfield, Vice President, Abiomed, Inc.

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September 17, 2010

Louis B. Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop C1-09-06
7500 Security Boulevard
Baltimore, Maryland 21244-1850

Dear Dr. Jacques:

Thank you for the opportunity to comment on the Centers for Medicare and Medicaid Services' (CMS's) proposed national coverage decision for Ventricular Assist Devices as Destination Therapy (CAG-00119R2). America's Health Insurance Plans (AHIP), the national association representing nearly 1,300 health insurance plans who provide coverage to more than 200 million Americans, is pleased to submit these comments on behalf of our members.

General Comments
AHIP supports CMS's efforts to ensure that all Medicare beneficiaries receive the most effective and appropriate treatments including approved medical devices based on current and valid scientific evidence for their use. AHIP and our members support CMS's proposed decision to provide coverage for ventricular assist devices (VADs) approved by the Food and Drug Administration (FDA) as a destination therapy and only for patients with New York Heart Association (NYHA) Class IV end-stage ventricular heart failure who are not candidates for heart transplant. Our members are also supportive of two out of the three proposed additional patient selection criteria: failure to respond to optimal medical management (including beta-blockers, and ACE inhibitors if tolerated) for at least 45 of the last 60 days, or have been balloon pump dependent for seven days, or IV inotrope dependent for fourteen days; AND demonstrate a functional limitation with a peak oxygen consumption of ? 14 ml/kg/min.

There are some questions regarding the clinical validity of the third proposed patient selection criteria; that a beneficiary must have a left ventricular ejection fraction (LVEF) < 25%. Many of our members' coverage policies for this device do not contain requirements for LVEF, as these patients are typically significantly ill when they meet the other stated criteria. In addition, plans are hesitant to set strict limitations on access to this technology for those patients who fall slightly outside of the <25% LVEF range, such as those with a 26-27% LVEF who could still benefit from this therapy. Therefore, we recommend that CMS consider removing or revising the patient selection criteria requiring a left ventricular ejection fraction (LVEF) < 25%.

Our members also continue to support the current NCD for Artificial Hearts and Related Devices (20.9) facility requirements that outline where this procedure needs to occur to be covered including:

• Facilities must have at least one member of the VAD team with experience implanting at least 10 VADs (as bridge-to-transplant or destination therapy) or artificial hearts over the course of the previous 36 months;
• Facilities must be a member of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS); and,
• By March 27, 2009, all facilities must meet the above facility criteria and be credentialed by the Joint Commission under the Disease Specific Certification Program for Ventricular Assist Devices (standards dated February 2007).

We also encourage CMS to include coverage for the "post-discharge kits" that are necessary for the use and maintenance of the device at home post-discharge from the hospital. These kits (which could include a belt, battery holster, shower kit, etc) should be considered an integral part of VAD placement, and should be provided to a patient in the hospital prior to discharge with instruction, and should not accrue a separate charge to the patient.

Thank you for the opportunity to comment on this important issue.

Sincerely,

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September 17, 2010

Louis B. Jacques, MD
Director
Coverage and Analysis Group
Center for Medicare & Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244

Re: Proposed NCD on use of ventricular assist devices as destination therapy (CAG-00119R2)

Dear Dr. Jacques:

The American College of Cardiology (ACC) and The Society of Thoracic Surgeons (STS) are pleased to submit comments on the proposed national coverage determination on Medicare’s coverage for the use of ventricular assist devices (VADs) as destination therapy. The ACC is a professional medical society and teaching institution made up of 39,000 cardiovascular professionals from around the world – including 90 percent of practicing cardiologists in the United States and a growing number of registered nurses, clinical nurse specialists, nurse practitioners, physician assistants and clinical pharmacists. STS is a not-for-profit organization representing almost 6,000 surgeons, researchers, and allied health professionals worldwide who are dedicated to ensuring the best possible heart, lung, esophageal, and other surgical procedures for the chest. We appreciate the opportunity to provide input on this important issue.

The ACC and STS strongly support the use of evidence-based medicine when making coverage determinations. Where the evidence supports expanded use of certain services, the ACC and STS generally encourage the expansion of coverage by Medicare, as well as by private insurance companies. In this case, based on a review of the evidence, both the ACC and STS support the proposal by the Centers for Medicare and Medicaid Services (CMS) not to expand coverage for the use of VADs as destination therapy for patients in New York Hospital Association (NYHA) functional Class IIIb patients. Both organizations believe that further study of these patients through clinical trials is warranted before coverage is expanded. Additionally, we believe that further distinction is needed within Class IIIb patients within the trials and that this population is not clearly appreciated as a distinct clinical entity by most physicians.

After 40 years of development, left ventricular assist devices (LVADs) were approved for support until transplantation. This approval was based on good outcomes during two to six months of support, compared only to outcomes of predominantly historical controls. For the greater burden of proof required for lifetime support, randomized trials have been required. These trials have shown that the pulsatile device prolongs survival compared to medical therapy, which usually included intravenous inotropic agents[1] and that the continuous flow device produced an added increment of survival in a similar patient population for which there was no direct medical control[2]. The benefit of the continuous flow device over medical therapy was assumed based on the equivalent outcome of the patients on pulsatile devices in both trials.

The two trials referenced above together have cleared the way for accelerated progress in mechanical circulatory support as lifetime therapy, particularly as more people can be helped than by transplantation, limited by the stagnant pool of donor hearts. The definition of “end-stage” has also evolved into profiles with specific therapeutic implications. Both trial data and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) have highlighted the obvious deficiencies of the NYHA class to correctly identify patients for prognosis and therapies. The Class IV designation encompasses five INTERMACS profiles with different baseline characteristics and outcomes[3]. Based on current experience, the target population for permanent support in Class IV patients can be reasonably expanded to include not only the Profile 1-3 inotrope-dependent patients typical of those in the trials[4], but also the INTERMACS profile 4, with resting symptoms on oral therapy at home, and some patients in Profile 5, with symptoms on minimal activity, if limitation is confirmed by peak oxygen consumption < 12 ml/kg/min. For groups in which imminent mortality is deemed sufficiently high [5], equipoise may not be sufficient to support a randomized medical control arm[6].

Trial data does not provide any basis of evidence for mechanical circulatory support in Class III patients. The vague characterization of Class III has yet to be crystallized into clinical phenotypes as has begun for Class IV. There is no validated division into Class IIIA, IIIB, and most heart failure physicians would have difficulty finding a reference for this specific classification or to define the specifics of this population. For instance, it is not clear how to classify the 31 patients who were not on intravenous inotropic therapy at the time of implantation of the continuous flow pump for destination therapy in the recent trial[2]. It seems unlikely that enrolled patients included patients profiles 1-3 and 6, while excluding the intermediate 4-5, unless by design. Available data indicates that they, in fact, derived a benefit similar to the 38 Class IV patients not on inotropic therapy in REMATCH, with baseline Minnesota Living with Heart Failure scores in the 70s and 40 percent one-year survival on medical therapy[4]. Similarity in the enrolled patients is further indicated by the superimposable early survival curves for pulsatile pump cohorts from the recent trial and the previous REMATCH trial.

Nor is there evidence for Class III patients from current clinical experience with approved devices. Even the experience with ambulatory Class IV on oral therapy is exceedingly limited (Table 2). Through September 2009, the total number implanted for lifetime support of ambulatory patients on oral therapy was only 26, including both the 19 declared as destination therapy and an additional 7 inserted in candidates unlikely to become eligible for transplant. Because of the heavy censoring for transplantation both early after implantation and for device complications in the bridge-to-transplant experience, it cannot bolster long-term outcome data for destination therapy.

It is important to position mechanical circulatory support appropriately in the spectrum of therapies for progressive heart failure. Both cardiac transplantation and mechanical circulatory support are currently considered as “replacement” therapies for Stage D heart failure, described in the guidelines as patients having “symptoms at rest or on minimal exertion, including profound fatigue; cannot perform most activities of daily living.”[7] Cardiac transplantation offers a survival of almost 60 percent at 10 years and relatively un-tethered quality of life. Although mechanical circulatory devices are not limited by supply, the current outcomes would not warrant consideration for patients considered too well for cardiac transplantation.

Thus, at this stage in the progress of mechanical circulatory support, it would not be considered either reasonable or necessary therapy for Class III patients, for whom trial populations on contemporary medical therapy show an anticipated survival of 70-80 percent at two years[5, 8- 10] (Table). A majority of heart failure patients surveyed did not anticipate considering an LVAD until life expectancy was less than 50 percent at one year. [11]. With a current 70 percent range of survival with devices, it is not clear that survival would be improved (Figure) for Class III patients; any benefit for Class III patients would be both absolutely and relatively small and occur later than seen for sicker patients. Quality and function would be relatively more important. However, many patients in Class III score in the 30s and 40s in the MLHF score, similar to that achieved with VADs[12, 13]. Patients with Class III symptoms generally describe reluctance to accept an up-front risk of mortality for a chance to improve later health [12]. In addition, any benefit in quality-adjusted life years would need to outweigh substantial risks. For example, the risk of stroke was 1-3 percent during two years in two recent trials of medical therapy for Class III-IV patients ([8, 10]), compared to 18 percent, or 13 percent annually, with the continuous flow pump[2]. To propose LVAD as permanent therapy for patients with Class III symptoms of heart failure not only exceeds the basis of evidence, but also may offer significant harm. At best, this is a position of equipoise between unknown outcomes[14], which is appropriately addressed only by rigorous scientific investigation with full disclosure of uncertainty prior to informed consent from the patients willing to participate. Further information will be offered by the planned REVIVE-IT trial, sponsored by the National Heart, Lung and Blood Institute.

Mechanical circulatory support is poised for accelerated progress. Fifty years of investigation, technical innovation, and personal sacrifice from the pioneering surgeons and brave patients have brought us to this threshold. However, the progress could be de-railed if current complication rates are reproduced without measured benefit in patients now enjoying reasonable quality of life on medical therapy.

Given the lack of evidence and the concerns described above, the ACC and STS support CMS’ proposal not to extend coverage for the use of VADs as destination therapy to patients in NYHA functional class IIIb heart failure. We appreciate the opportunity to provide these comments and look forward to working with CMS on future coverage issues. Please direct any questions or concerns to Lisa P. Goldstein at (202) 375-6527 or lgoldstein@acc.org

Sincerely,

/s/
Ralph G. Brindis, M.D., M.P.H., F.A.C.C.
President
American College of Cardiology

/s/
Douglas J. Mathisen, M.D.
President
Society of Thoracic Surgeons

Table 2

Figure 1

1. Rose, E.A., et al., Long-term Use of a Left Ventricular Assist Device for Endstage Heart Failure. N Engl J Med, 2001. 345(20): p. 1435-1443.
2. Slaughter, M.S., et al., Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med, 2009. 361(23): p. 2241-51.
3. Stevenson, L.W., et al., INTERMACS profiles of advanced heart failure: the current picture. J Heart Lung Transplant, 2009. 28(6): p. 535-41.
4. Stevenson, L.W., et al., Left ventricular assist device as destination for patients undergoing intravenous inotropic therapy: a subset analysis from REMATCH (Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure). Circulation, 2004. 110(8): p. 975-81.
5. Lindenfeld, J., et al., Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association class IV heart failure. Circulation, 2007. 115(2): p. 204-12.
6. Stevenson, L.W. and R.L. Kormos, Mechanical Cardiac Support 2000: Current Applications and Future Trial Design. J Am Coll Cardiol, 2001. 37: p. 340-370.
7. Hunt, S.A., et al., ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation, 2005. 112(12): p. e154-235.
8. Pitt, B., et al., The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med, 1999. 341(10): p. 709-17.
9. Packer, M., et al., Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation, 2002. 106(17): p. 2194-9.
10. Bristow, M., Beta-adrenergic receptor blockade in chronic heart failure. Circulation, 2000. 101: p. 558-569.
11. Stewart, G.C., et al., Thresholds of physical activity and life expectancy for patients considering destination ventricular assist devices. J Heart Lung Transplant, 2009. 28(9): p. 863-9.
12. Stevenson, L.W., et al., Changing preferences for survival after hospitalization with advanced heart failure. J Am Coll Cardiol, 2008. 52(21): p. 1702-8.
13. Abraham, W.T., et al., Cardiac resynchronization in chronic heart failure. N Engl J Med, 2002. 346(24): p. 1845-53.
14. Djulbegovic, B., Acknowledgment of uncertainty: a fundamental means to ensure scientific and ethical validity in clinical research. Curr Oncol Rep, 2001. 3(5): p. 389-95.
15. Taylor, A.L., et al., Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med, 2004. 351(20): p. 2049-57.
16. Bristow, M.R., et al., Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med, 2004. 350(21): p. 2140-50.

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We are encouraged CMS is proposing to approve most of the requests made to expand coverage for patients eligible for Destination Therapy. These changes should provide greater access to patients with late-stage heart failure, as they would effectively expand coverage to all Class IV patients studied in the HeartMate II Destination Therapy trial. The proposed changes to CMS’ current National Coverage Decision include:

The decision not to include class IIIB patient in the coverage for Destination Therapy based on the published literature denies the clinical reality. The accepted changes, especially that the VO2max should be below or equal to 14 can be frequently found in patients who clinicians call "frequent flyers", patients who wander between Class III and IV and are best described by IIIB. These are the patients which are admitted to hospitals with tremandeous costs associated where mechanical assist will help to reduce these. This is the same population Medicare will deny coverage if readmitted within 30 days. I see a catch 22 in developments and ask to reconsider your decision.

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I am concerned for the requirement for MVO2 as it is written.

b. Have a left ventricular ejection fraction (LVEF) < 25%; and,c. Have demonstrated functional limitation with a peak oxygen consumption of 14 ml/kg/min.

For the patients with whom the new proposal includes:

a. Have failed to respond to optimal medical management (including beta-blockers, and ACE inhibitors if tolerated) forat least 45 of the last 60 days, or have been balloon pump dependent for 7 days, or IV inotrope dependent for 14 days;and,

They may not have had a previous MVO2, and certainly would not be able to undergo that thest in their current condition. I would propose the laguage be changed to "and/or" for the end of line B. Thank you.

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