Transcatheter Tricuspid Valve Replacement (TTVR)

Dear CMS,

We appreciate the opportunity to emphasize the significance of a National Coverage Decision for Transcatheter Tricuspid Valve Repair (TTVR). The compelling data on TTVR highlights not only the clinical efficacy but also the profound impact on patients' lives. Studies have consistently shown that TTVR significantly improves symptoms and dramatically enhances the quality of life for individuals suffering from severe symptomatic tricuspid regurgitation. These improvements are not just statistical; they translate into tangible benefits for patients, allowing them to engage more fully in daily activities and reducing the burden on caregivers and the healthcare system. A positive coverage decision would ensure broader access to this life-changing treatment, aligning with CMS's mission to promote high-quality, effective healthcare for all beneficiaries.

Sincerely,
Carlos E Sanchez, MD

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CAG-00467N Transcatheter Tricuspid Valve Replacement (TTVR)

Dear Centers for Medicare and Medicaid Services,

The prevalence of significant tricuspid regurgitation is high and the morbidity and mortality stemming from it are substantial. Beyond diuretics, there is little to offer in the way of medical therapy and surgery is uncommonly performed for these patients given its high risk and frequent complications. In this context, the arrival of an effective minimally invasive, catheter-based procedure addresses a large unmet clinical need. While the data are incomplete and long-term outcomes unknown, early results are very promising and transcatheter tricuspid valve replacement (TTVR) is a welcome new treatment option.

In setting guidelines for evaluation of patients with tricuspid regurgitation and performance of TTVR, both clinical expertise and patient access must be considered and prioritized. Overly onerous requirements that don’t increase safety will only serve to drive up costs and unnecessarily slow evaluation/treatment times and limit access.

From a multidisciplinary team representing all key stakeholders in this decision, here are recommendations regarding the evaluation, treatment, and management of patients with TR being considered for and treated with TTVR:

Under care of a heart team: borrowing the words of the mitral TEER NCD: “The patient (preoperatively and postoperatively) is under the care of a heart team: a cohesive, multidisciplinary, team of medical professionals. The heart team concept embodies collaboration and dedication across medical specialties to offer optimal patient-centered care.” The heart team must include the following members with experience and training as specified: (1) interventional cardiologist with expertise in the structural heart valve procedures; (2) cardiac surgeon with expertise in heart valve disease; and (3) interventional echocardiographer (cardiologist or anesthesiologist) with expertise in structural heart valve procedures. When needed, the team should also include an electrophysiologist and heart failure cardiologist experienced in treating patients with advanced heart failure.

Pre-procedure evaluation: Each patient's suitability for TTVR must be evaluated, documented, and made available to other heart team members. A face-to-face evaluation and examination by a TTVR implanter (cardiologist or surgeon) or TTVR interventional echocardiographer is required. The heart team should review and discuss patients considered for TTVR to form a multidisciplinary recommendation.

TTVR procedure requirements: A cardiac surgeon should NOT be specifically required to participate in the case. The TRISCEND trial did not require a cardiac surgeon to participate in the procedures and most/many sites did not have a cardiac surgeon participate in the procedure. The data from that trial are what form the basis for the FDA approval of the device, so there is no solid rationale for requiring a cardiac surgeon in the procedure when the trial did not. The following language (with minor modification) from the mitral TEER NCD would seem to be appropriate for TTVR:

- An interventional cardiologist OR cardiac surgeon from the heart team must perform the TTVR and an interventional echocardiographer from the heart team must perform transesophageal echocardiography during the procedure (unless the procedure can be done with intracardiac echocardiography). The interventional cardiologist and cardiac surgeon (or 2 interventional cardiologists or 2 cardiac surgeons) may jointly participate in the intra-procedural technical aspects of TTVR as appropriate. All physicians who participate in the procedure must have device-specific training as required by the manufacturer.

Thank you for considering these comments.

Sincerely,

Brian R. Lindman, MD, MSc
Medical Director, Structural Heart and Valve Center
Vanderbilt University Medical Center

Colin M. Barker, MD
Section Chief, Interventional Cardiology
Director, Cardiac Catheterization Laboratory
Vanderbilt University Medical Center

Kashish Goel, MD
Director, Transcatheter Heart Valve Interventions
Vanderbilt University Medical Center

Tarek Absi, MD
Surgical Director, Structural Heart and Valve Center
Vanderbilt University Medical Center

Frederick W. Lombard, MBChB
Division Chief, Cardiothoracic Anesthesia
Vanderbilt University Medical Center

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July 1, 2024

Tamara Syrek Jensen, JD
Director, Coverage & Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Blvd.
Baltimore, MD 21244

Re: CAG-00467N Transcatheter Tricuspid Valve Replacement (TTVR)

Dear Ms. Syrek Jensen,

Edwards Lifesciences (“Edwards”) is pleased with the opening of the National Coverage Analysis (NCA) for Transcatheter Tricuspid Valve Replacement (TTVR). Edwards believes that the posting of the Tracking Sheet is an important step towards securing timely and equitable patient access to life-changing medical innovation. Patients with tricuspid regurgitation (TR) suffer from debilitating symptoms and currently have limited or no therapeutic treatment options; patients and physicians are eagerly seeking use of this U.S. Food and Drug Administration (FDA)Designated Breakthrough device, which can be facilitated via the completion of a Medicare national coverage determination (NCD).

We appreciate the opportunity to submit comments on the TTVR NCA, which expands on topics covered in our NCD request letter and support transparency in the coverage process. Our comments focus on three areas:

• CMS/FDA Parallel Review of the Edwards EVOQUE System
• Principles for TTVR Medicare Coverage Policy
• Recommendations for TTVR Medicare Coverage Policy

In summary, Edwards believes that with the completion of the Evidence Preview, approval of the Evidence Development Plan, and the posting of the Tracking Sheet, CMS should move quickly to the next step of issuing the Proposed Decision Memo in alignment with the intent of the Parallel Review program. As CMS considers the coverage parameters for TTVR, we urge the Agency to consider four key principles:

• Enabling timely and equitable access for Medicare beneficiaries while minimizing patient burden;
• Balancing flexibilities for hospitals and clinicians while optimizing patient outcomes;
• Durability of coverage policy during evidence generation; and
• Commitment to ongoing evidence generation.

I. CMS/FDA Parallel Review of the Edwards EVOQUE System

Edwards was accepted into the Parallel Review Program on May 21, 2020. Under the Parallel Review Program, there was concurrent review by CMS and the FDA of the Premarket Approval (PMA) submission for the Edwards EVOQUE tricuspid valve replacement system (EVOQUE system) with the goal of “prompt and efficient patient access” for Medicare beneficiaries.(1)

On February 1, 2024, the FDA completed its review of the PMA application and approved the EVOQUE system for the improvement of health status in patients with symptomatic severe tricuspid regurgitation despite optimal medical therapy, for whom tricuspid valve replacement is deemed appropriate by a Heart Team. As stated by the FDA in its press announcement on the EVOQUE system approval: “[t]his approval marks the first transcatheter replacement device indicated for use in the tricuspid position.”(2)

The results from the Breakthrough Pathway Cohort of the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device (“TRISCEND II Pivotal Trial”) were the basis for the FDA approval of the EVOQUE system. Successful six-month results were presented at the Transcatheter Cardiovascular Therapeutics (TCT) Conference in 2023. These results showed favorable safety and effectiveness outcomes, demonstrating superiority to optimal medical therapy (OMT) alone and meeting all primary endpoints. Key findings in the trial included significant reduction or elimination of tricuspid regurgitation and significant and sustained quality of life improvement, while demonstrating a favorable balance between risk and benefit. A summary of the clinical evidence for TTVR was provided in our NCD request, which is linked in the TTVR Tracking Sheet, and can also be found in the Summary of Safety and Effectiveness Data (SSED) on the FDA website.

The TTVR Tracking Sheet specifies that the NCA will analyze “the clinical evidence for characteristics or comorbidities that make patients more or less likely to benefit from the device and whether specific treatment conditions are necessary to achieve the outcomes demonstrated in clinical studies. Other outcomes of interest may include decreased mortality, decreased frequency of exacerbations requiring emergency room or hospital admission, improved function, and quality of life.”

Under Parallel Review, CMS assessed these topics outlined in the Tracking Sheet over the course of the last year. The process applied the principles and processes that are outlined in the Proposed Guidance documents that were released in June 2023 for the Transitional Coverage for Emerging Technologies (TCET) pathway, National Coverage Analysis Evidence Review, and Coverage with Evidence Development (CED). The process required the following:

• Evidence Preview – This CMS-generated document summarizes a systematic literature review that provides CMS’s feedback on the strengths and weaknesses of the publicly available evidence for the EVOQUE system at the time the review was conducted. In its review, CMS assessed the topics that have then been articulated in the TTVR Tracking Sheet, posted June 20, 2024. The Evidence Preview for EVOQUE was finalized by CMS in December 2023.

• Evidence Development Plan (EDP) – As defined in the TCET proposed guidance, the purpose of this sponsor-generated document is to articulate to CMS the planned body of evidence for a technology that will address the evidence needs under CED. The intent is to estimate the timepoint in the future at which there would be sufficient evidence for CMS to move from transitional coverage to “durable coverage” (i.e., coverage without the requirement for evidence development). The EDP for EVOQUE outlines Edwards’ plan for conducting and reporting on clinical and real-world evidence studies to fulfill the requirements for CED. The EDP for EVOQUE was approved by CMS and the Agency for Healthcare Research and Quality (AHRQ).

Edwards believes that with the completion of the Evidence Preview, approval of the Evidence Development Plan, and the posting of the Tracking Sheet, CMS should move quickly to the next step of issuing the Proposed Decision Memo in alignment with the intent of the Parallel Review program of “facilitating earlier access to innovative medical technologies for Medicare beneficiaries.”(1) To date, two technologies have completed the Parallel Review Program. In both instances, CMS issued the Tracking Sheet and the Proposed Decision Memo together. For the first technology to successfully complete the Parallel Review Program, Exact Sciences’ Cologuard, FDA approved the medical device on August 11, 2014. On the same day, CMS initiated its NCA. CMS published a final NCD establishing coverage on October 9, 2014, less than 2 months after the medical device received its premarket approval.1 Edwards recognizes the difference in timing of our Parallel Review technology, mainly that CMS required the completion of the Evidence Preview and EDP prior to issuing a Proposed Decision Memo. The TCET Proposed Guidance states CMS’ goal is to finalize an NCD for technologies accepted into and continuing in the TCET pathway within 6 months after FDA market authorization. That date for EVOQUE would be August 1, 2024.

Below is a summary of Edwards’ principles for developing a coverage policy and the recommendations for the TTVR coverage policy that we respectfully request CMS consider in the development of its draft coverage policy.

II. Principles for TTVR Medicare Coverage Policy

In the United States, more than 1.6 million people suffer from significant TR (moderate and above).(3,4) The prevalence of moderate or greater TR is more frequent in women than men, with approximately four times as many women with the disease.(5) The prevalence of TR increases with age and the incidence of TR is expected to increase with an aging population.(6)

In the absence of clinical guidelines recommending isolated tricuspid valve surgical replacement, most patients with TR are medically managed for their symptoms and are not treated for the underlying disease.(7,8) The EVOQUE system was the first FDA approved TTVR technology indicated for the improvement of health status in patients with symptomatic severe TR despite being treated optimally with medical therapy for whom tricuspid valve replacement is deemed appropriate by a Heart Team. As an FDA Designated Breakthrough device, the EVOQUE system creates new hope for patients for whom no other treatment options previously existed. Susheel Kodali, MD, director, Structural Heart and Valve Center at Columbia University Irving Medical Center/New York-Presbyterian Hospital and TRISCEND II Study Principal Investigator, states:

In our submission of the NCD request for TTVR under the Parallel Review program, Edwards considered the impact of the criteria for coverage of this innovative technology on the many Medicare beneficiaries without alternatives. As CMS considers the coverage parameters for TTVR, we urge the Agency to consider four key principles:

• Enabling timely and equitable access for Medicare beneficiaries while minimizing patient burden;
• Balancing flexibilities for hospitals and clinicians while optimizing patient outcomes;
• Durability of coverage policy during evidence generation; and
• Commitment to ongoing evidence generation.

The paramount goal for a national coverage policy is to achieve the balance of facilitating timely patient access to treatment while optimizing patient outcomes. Patients with TR suffer from significant and frequent symptoms affecting their everyday lives, including edema, ascites, shortness of breath, and chest pain. Patients with TR not only experience the significant burden from this disease, but frequently suffer from multiple comorbidities, including atrial arrhythmias, hyperlipidemia, ischemic heart disease, and diabetes.(8) The patient population with severe TR is highly symptomatic, unable to participate in everyday activities.

To better understand the goals of the patients with TR in seeking treatment, Edwards incorporated a patient preference survey into the TRISCEND II pivotal trial. For 53% of patients who were treated with EVOQUE, caring for themselves was the most important activity following treatment.(10) Patients also ranked visiting friends and family, walking one block, and climbing stairs as priority activities they were unable to do prior to treatment and were seeking to improve.

In developing coverage parameters, CMS can alleviate unnecessary burdens on this patient population and their families by ensuring each coverage requirement optimizes the care pathway to treatment. Below we present how coverage requirements such as defining the eligible patient population, hospital volume requirements, and the Heart Team and patient evaluation requirements may impact patient access.

Eligible Patient Population: Implications for Patient Access

Results from the TRISCEND II Pivotal Trial were the basis for the FDA approval of the EVOQUE system (a summary of the trial results can be accessed in the FDA Summary of Safety and Effectiveness). During the design of the pivotal trial, specific inclusion and exclusion criteria were critically evaluated. Notably, for participation in the study, patients were not required to be ineligible for tricuspid valve surgery. This decision was largely based on the absence of clinical guidelines recommending isolated surgical intervention and the need to treat the patient population most likely to benefit.

CMS must ensure that coverage for TTVR is consistent with the experience to date and the patient population meeting FDA labeling criteria. As such, Edwards recommends CMS cover TTVR according to the FDA-approved indication for the EVOQUE system. Without access to the EVOQUE system, an FDA Designated Breakthrough device, this patient population suffering from a debilitating disease will not have access to treatment options.

Hospital Volume Requirements: Implications for Patient Access

In the early stages of a novel technology, hospital volume requirements serve as a proxy for identifying the facilities that have the infrastructure and clinical expertise necessary to ensure positive patient outcomes, procedural safety, and clinical success. As CMS establishes the requirements for hospitals to be eligible to perform the procedure, there will be implications on where beneficiaries can seek out this care and how far they must travel.

The burden of the distance traveled to a hospital providing the needed treatment can significantly impact a patient’s access to care. As has been demonstrated in cancer treatment, as patients travel greater distances to receive care, the disease is more advanced at diagnosis and prognoses and quality of life worsen. The threshold for these poorer outcomes was more than 50 miles or over one hour of travel time.(11) The lack of public transportation and significant physical travel distances are even more acutely felt by a patient population burdened with severe symptoms. Patients participating in the clinical trial were not all located near the trial sites. Some patients reported driving several hours for each visit, having to manage through the physical challenges of lengthy travel. Restrictive hospital volume requirements in a coverage policy will directly correlate with beneficiaries’ ability to access care.

There are unintended consequences of overly restrictive hospital volume requirements on equitable patient access to innovative technologies. For example, research found that during the initial growth phase of transcatheter aortic valve replacement (TAVR) programs in the United States, hospitals serving wealthier patients were more likely to start programs.(12,13) This pattern of growth has led to inequities in the dispersion of TAVR, with lower rates in poorer communities, despite the treatment having been associated with lower mortality rates in patients for whom TAVR would be appropriate.(14) This may be a part of ongoing geographic and socioeconomic disparities in care.(15,16,17)

Distance to the hospital not only impacts the patient, but also the caregivers, family, and friends supporting the patient. Even prior to seeking treatment, caregiver strain increases as patient symptoms worsen. Increasing the distance required to travel for TR treatment further exacerbates this strain and may require overnight stays and time off from work by caregivers.

Edwards evaluated the potential impact of hospital volume requirements for TTVR, specifically to assess the impact on Medicare beneficiaries. Using the Transcatheter Edge-to-Edge Repair for Mitral Valve Regurgitation (M-TEER) hospital volume requirements as an example, we evaluated the impact of requiring hospitals to perform at least 20 M-TEER procedures per year to be eligible to perform TTVR. This requirement results in more than a quarter of Medicare beneficiaries without access (i.e., living in a zip code more than 50 miles from the nearest eligible TTVR hospital). Similarly, of all low-income zip codes, 89% would not have access to TTVR under these hospital volume requirements.

Edwards recommends CMS require hospitals to meet either of the volume requirements outlined in (A) or (B):

This proposed approach, as compared to = 20 M-TEER as a hospital volume requirement, balances the need for patient access with hospital characteristics we believe support positive patient outcomes. Under this proposal, more than 10 million more beneficiaries, a segment of which has TR, would be in geographic proximity to a hospital eligible to provide TTVR. Further, while this approach reduces the disparate impact on low-income beneficiaries by half, Edwards urges CMS to evaluate how other components of this policy can increase access to care for underserved populations.

Table 1. Impact of hospital volume requirements on Medicare beneficiary access

	≥ 20 TEER per year	Edwards’ recommendation
Percent of beneficiaries without access:	26.7%	7.2%
Percent of low-income ZIP codes without access:	89%	78%

(Without Access: ZIP codes > 50 miles from the nearest eligible hospital zip code. Source: Definitive HealthCare, 2022. U.S. Census Data, 2020.)

While the impact on patient access is critical to consider when establishing coverage parameters, hospital volume requirements must also appropriately identify hospitals with the experience and infrastructure necessary to successfully perform TTVR. Our recommended hospital volume requirements ensure hospitals performing TTVR have the following necessary experience:

• Transcatheter procedural experience;
• Transcatheter imaging experience; and
• Understanding of the tricuspid valve.

Both M-TEER and TAVR coverage policies require hospitals to have experience providing the corresponding surgical intervention. However, in both cases, surgical experience with each valve was necessary with the introduction of the procedures, as surgery was the only alternative treatment option for the given patient population. Isolated tricuspid valve surgery is rarely performed and is not guideline-directed for patients with TR. As such, we only propose to incorporate explicit tricuspid valve surgical experience into criteria (B), referenced above, and should not be required for a hospital to be eligible to perform TTVR.

Heart Team and Patient Evaluation for TTVR: Implications for Patient Access

Due to the nature of their disease and number of comorbidities, patients with severe TR who are referred by their cardiologists for treatment require intense and frequent healthcare. Based on an internal analysis of an administrative claims and electronic health records database, Edwards estimates that in the first year of being diagnosed with symptomatic, severe TR, a patient has approximately 12 physician office visits. Over the next two years, an untreated patient with symptomatic severe TR will likely at least maintain this same level of healthcare utilization. As such, to reduce the burden on a patient population suffering debilitating symptoms, evaluations for TTVR should be focused and targeted on determining suitability for TTVR.

In determining suitability for TTVR, it is important that either the interventional cardiologist OR the cardiac surgeon on the Heart Team evaluate the patient for anatomical considerations impacting procedural success, such as leaflet morphology, annular dilatation, or right ventricular function. Edwards recommends CMS take a targeted and thoughtful approach in requiring patient evaluation for TTVR. While patient evaluation is critical to ensure effective treatment of TR, overly burdensome evaluation requirements may deter patients from seeking care and may be unnecessary in an already overburdened healthcare system.

After conducting the patient evaluation, the interventional cardiologist or cardiac surgeon on the Heart Team will provide a treatment recommendation to the Heart Team. The Heart Team will guide the treatment of the patient who has been referred for TTVR, in coordination with subspecialists.

As per the 2019 AATS/ACC/ASE/SCAI/STS Expert Consensus Systems of Care Document: A Proposal to Optimize Care for Patients With Valvular Heart Disease, Heart Teams have emerged as the standard of care in managing patients with valvular heart disease and ensure a multi-disciplinary approach to managing structural heart patients pre-, peri-, and post-operatively.(19) The Heart Team approach combines the knowledge of multiple disciplines, such as interventional cardiology, cardiac surgery, and interventional imaging.

Once a patient is identified as a candidate for TTVR, the Heart Team assesses if other specialty consultations are needed, such as consultation with an electrophysiologist for a patient with a pre-existing pacemaker or with a nephrologist for a patient with chronic kidney disease. In current clinical practice and as recommended in the multi-society consensus for treatment of patients with valvular heart disease, Heart Teams regularly consult with specialists as needed.(19)

Edwards endorses the continued and evolving role of the Heart Team and encourages hospitals to consider how to alleviate burdens on both clinicians and patients, where possible. To support this effort, CMS should implement a coverage policy providing flexibilities, where clinically appropriate, in recognition of the relative maturity of Heart Teams.

As CMS considers the coverage policy options for TTVR, we urge the Agency to consider the evolution of clinical practice as it relates to transcatheter therapies. The first transcatheter NCD was implemented in 2012 for the coverage of TAVR. The introduction of this novel transcatheter technology, along with the NCD, drove hospital infrastructure to adapt to providing transcatheter technologies, and clinical practice to evolve to improve outcomes. This once novel procedure has since become a well-established treatment modality that improves the lives of approximately 100,000 patients each year in the United States.(20) Similarly, mitral valve transcatheter technologies and other transcatheter therapies have been incorporated into clinical practice and strengthened the infrastructure of transcatheter procedure offerings in hospitals across the country.

Heart Teams: Flexibilities for Hospitals and Clinicians

As noted above, hospitals experienced in transcatheter cardiac procedures have mature and well-defined Heart Teams that play a critical role in managing the pre-, peri-, and post-operative care of the patient.

Flexibility in the composition of the Heart Team ensures that finite hospital resources are used appropriately, and each patient receives the most appropriate care. Each patient with TR is unique, with different symptoms, comorbidities, and patient preferences in their treatment. As such, the Heart Team involvement must be calibrated for different patients. For example, the Heart Team caring for a patient with a pre-existing pacemaker or pre-existing conduction system disease may require consultation with an electrophysiologist. However, requiring an electrophysiologist be present for every TTVR case during Heart Team discussions will cause delays in access to treatment. Hospitals should maintain discretion to determine the members of the Heart Team clinically necessary to care for patients undergoing TTVR.

Intra-Procedural Operators: Flexibilities for Hospitals and Clinicians

The greatest clinical experience with TTVR has been performed within the context of the TRISCEND II Pivotal Trial. The protocol for the trial did not require an interventional cardiologist and cardiac surgeon to jointly perform the intra-operative components of the TTVR, which has since been reflected in early commercial experience. As such, Edwards recommends CMS implement a coverage policy that requires either an interventional cardiologist or cardiac surgeon perform the intra-operative aspects of TTVR, permitting a second operator when appropriate.

This approach is currently incorporated into the M-TEER coverage policy, in which the policy allows but does not require two operators. The policy states that a second operator may jointly participate in the procedure, as appropriate. Accordingly, some hospitals mandate two physicians jointly perform the M-TEER procedure. This flexibility in coverage policy has ensured that hospitals do not spend redundant resources when not clinically appropriate to ensure patient safety and procedural success. It has also helped to reduce potential barriers due to logistical challenges (e.g., staffing or scheduling) for patients where delays in care may have clinical implications.

Requiring two operators to perform the intra-operative aspects of TTVR may negatively impact patient access to the procedure. Over time, as the procedure matures and procedural demand increases, concurrent shortages of cardiology physicians and thoracic surgeons may present a hurdle to access. The Health Resources & Services Administration (HRSA) anticipates a 15% and 24% shortfall of cardiology physicians and thoracic surgeons, respectively, by 2030, which will continue to worsen.(21) Additional requirements for two operators to participate in the intra-operative aspects of TTVR may delay care for patients seeking TTVR, as well as for patients requiring other care furnished by these specialists.

As both the interventional cardiologist and cardiac surgeon are core members of the Heart Team at every hospital, we believe the collaboration amongst specialists will be maintained in the absence of requiring both to perform the TTVR procedure, and that when patient or institutional needs are better served by two operators this option is preserved.

An NCD is expected to be in place for several years before it is reconsidered. Furthermore, the NCD will apply to beneficiaries insured under Medicare fee-for-service as well as under Medicare Advantage (MA); as of 2024, there are nearly 70 million Medicare beneficiaries in total. Thus, the NCD will be in place for a significant duration of time with relevance for a significant portion of the total US population.

Edwards believes the NCD for TTVR should be appropriate for the entire duration of the NCD. Coverage parameters should optimize patient outcomes and ensure prudent dispersion of the technology, while allowing adequate flexibility for the technology to grow and be adopted throughout the entire duration of the NCD. Edwards estimates that the NCD will be reconsidered in 7+ years, due to the current estimates for when the EVOQUE CED study could be completed, and at which point CMS may have the evidence necessary to establish durable coverage. Edwards believes the NCD should be appropriate for the entire 7+ year period.

Eligible Patient Population: Durability of Coverage

One example of how to build flexibility into the NCD is to establish coverage for TTVR when furnished according to an FDA-approved indication instead of explicitly specifying the current indications for use within the policy itself, which is consistent with all previous transcatheter NCDs. This allows the policy to comprehend any changes in the indications without having to reopen the policy, a process that can be lengthy and resource-intensive for CMS and for all involved stakeholders.

Hospital Volume Requirements: Durability of Coverage

Another example of how to build flexibility into the NCD is to establish hospital volume requirements that allow for the technology to be adopted by hospitals that serve broader patient populations than is currently available in the early days of adoption. We believe this NCD under CED should have the appropriate coverage parameters that allows for the continuation of good outcomes and broader adoption for the future. TTVR is currently offered in a limited number of hospitals as hospitals and clinicians gain experience and awareness of the therapy and as Edwards, as the manufacturer, provides the training and support necessary for performing the procedure. In five years, for instance, the maturity of transcatheter programs and awareness of the therapy will have grown, and a broader swath of hospitals will be ready to adopt the procedure. It is important that the coverage policy does not prohibit such adoption. The consequence of this constraint will be patients who are unable to receive treatment for their disease, and potentially inequitable diffusion of the technology, further exacerbating health disparities among underserved populations.

Experience under the NCDs for TAVR and M-TEER indicates that adjusting hospital volume requirements does not lead to rapid growth in the number of hospitals offering the technology; rather, for those technologies there was a steady addition of hospitals offering the therapies despite changes in hospital volume requirements. This is partly due to the rigorous training and experience requirements mandated by Edwards. Unnecessary coverage parameters should be avoided and limit patient access.

Edwards is committed to ongoing evidence generation for the EVOQUE system. In the coming years, Edwards plans to continue reporting follow-up data from the TRISCEND II Pivotal Trial, conducting planned studies using real-world data and executing a post-approval study. Edwards anticipates a broad body of evidence, both sponsored by Edwards and others, will be published over the next several years prior to a reconsideration for durable coverage by CMS. The Society for Thoracic Surgeon (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapies (TVT) Registry has robust data collection that will support a broad body of evidence related to TTVR. In the first 5 years of the TAVR NCD with CED, there were 41 studies published using the TVT Registry data. As demonstrated by the TAVR experience, there is great interest and commitment among the cardiovascular community to grow the body of evidence for novel technologies. Since the Evidence Preview was completed in 2023, there have already been numerous publications related to TR and TTVR. In the last month alone, there have been two publications that provide important information about TR and therapies to treat TR.(22,23)

Coverage with Evidence Development

As a company dedicated to ongoing innovation and evidence generation, Edwards is aligned with CMS’ objectives of improving health outcomes while delivering greater value through an evidence-based coverage policy. Edwards supports an NCD with CED as the coverage pathway for EVOQUE, as timely access to this technology is critical for Medicare beneficiaries with TR. Coverage under the CED pathway is aligned with the principles of Breakthrough technologies, enabling patient access to critical therapeutic options while ensuring ongoing evidence generation.

Consistent with the process articulated in the Proposed Guidance documents for TCET and CED, CMS requires the manufacturer to develop a fit-for-purpose evidence plan for addressing research questions for CED. As such, Edwards submitted a protocol for a study that will use real-world data to fulfill the CED requirements. This study will provide critical insight on the real-world outcomes for TTVR, including outcomes for sub-populations such as sex and race. The completion of this study will serve as the primary basis for a reconsideration of the coverage policy.

Requiring CED studies to have written fully executable protocols aligned with CMS-identified technology-specific research questions creates additional transparency and accountability for evidence generation. We agree with the approach, as outlined in TCET, that all manufacturers with technologies covered under an NCD with CED should be actively participating in the ongoing evidence generation related to a procedure as outlined in the technology-specific EDP.

Further, we support that each technology have its own Evidence Preview conducted by CMS, from which CED research questions may be based. In preparation for coverage of TTVR, the Evidence Preview literature review was specific to publications related to EVOQUE, limiting its applicability to other TTVR technologies. Additionally, it was critical to have the completed Evidence Preview prior to developing the EVOQUE EDP.

Even within a class of similar medical devices, each technology is unique in its target patient population, mechanism of action, and potential adverse events. For example, the EVOQUE valve uses nine anchors to capture the native tricuspid valve leaflets for positioning and deployment. However, other TTVR technologies currently being investigated for the treatment of symptomatic severe tricuspid regurgitation have unique attributes and mechanisms of action.(24) While these technologies intend to treat a similar patient population, during a period of coverage under CED, real-world evidence generation should be required for each of these technologies, answering questions specific to each.

Non-FDA Approved Indications

Coverage for technologies within the context of additional clinical trials provides a pathway for ongoing innovation, benefitting patients and clinical outcomes. Additional clinical study is critical for deepening the evidence base for a technology, potentially in expanded indications in populations that would not meet the criteria for coverage and would require findings in these studies to be publicly reported.

III. Recommendations for TTVR Medicare coverage policy

Edwards has developed recommendations for a coverage policy for TTVR, which are summarized in the table below. These recommendations were developed based on the principles of:

• Enabling timely and equitable access for Medicare beneficiaries while minimizing patient burden;
• Balancing flexibilities for hospitals and clinicians while optimizing patient outcomes;
• Durability of coverage policy during evidence generation; and
• Commitment to ongoing evidence generation.

NCD Requirement	Recommendation
Patient population	Coverage to label
Hospital volume requirements	EITHER (A) or (B) A. ≥ 20 mitral or tricuspid valve procedures per year or = 40 over two years, of which at least 10 (or 20 over two years) must be transcatheter valve procedures B. ≥ 5 tricuspid valve surgical procedures per year AND = 10 transcatheter valve (any) procedures
Patient evaluation	Either the cardiac surgeon OR an interventional cardiologist experienced in the care and treatment of tricuspid regurgitation must document each patient’s suitability for TTVR
Heart Team	Cardiac surgeon Interventional cardiologist Interventional echocardiographer Physician with cardiology experience treating patients with tricuspid regurgitation, including advanced heart failure associated with tricuspid valve disease Providers from other physician groups, such as electrophysiology, when necessary, as well as advanced patient practitioners, nurses, research personnel, and administrators
Operator requirements (experience)	Interventional Cardiologist: ≥ 30 career structural heart disease procedures Cardiac Surgeon: ≥ 20 mitral valve surgical procedures per year, or = 40 over two years Interventional Echocardiographer: ≥ 30 career structural heart procedures
Operator requirements (intra-procedure)	An interventional cardiologist or cardiac surgeon from the Heart Team must perform the TTVR. A second physician may jointly participate in the intra-operative technical aspects of TTVR, as appropriate, as determined by the Heart Team
CED	Requires approval of CED study upon submission of written protocol addressing CED questions
Non-FDA approved indications	Requires approval of clinical study upon submission of written protocol addressing CED questions

As we have demonstrated in our long history of bringing innovative therapies to patients with Medicare coverage, Edwards is committed to the process CMS has defined for such technologies under the NCD with CED pathway. We are acutely aware of the unmet need for patients with TR and encourage CMS to move swiftly and carefully to the next step of establishing a national coverage policy for TTVR, enabling patients’ timely access to this innovation. Thank you for your consideration of our comments.

Sincerely,

/s/
Daveen Chopra
Corporate Vice President and General Manager, Transcatheter Mitral and Tricuspid Therapies (TMTT)
Edwards Lifesciences

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(1) 81 Federal Register 73114, (October 24, 2016).
(2) U.S. Food and Drug Administration. FDA Roundup: February 2, 2024.
(3) Stuge O, Liddicoat J. Emerging opportunities for cardiac surgeons within structural heart disease. J Thorac Cardiovasc Surg. Dec 2006;132(6):1258-61. doi:10.1016/j.jtcvs.2006.08.049
(4) Singh JP, Evans JC, Levy D, et al. Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study). The American journal of cardiology. 1999;83(6):897-902.
(5) Hahn R. Tricuspid Regurgitation. N Engl J Med 2023;388:1876-91. doi:10.1056/NEJMra2216709
(6) Utsunomiya H, Itabashi Y, Mihara H, et al. Functional Tricuspid Regurgitation Caused by Chronic Atrial Fibrillation. Circulation: Cardiovascular Imaging. 2017;10(1):e004897. doi:10.1161/CIRCIMAGING.116.004897
(7) Otto C, Nichimura R, Bonow R, et al. 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2021;143:e72-e227. doi:10.1161/CIR.0000000000000923
(8) Chorin E, Rozenbaum Z, Topilsky Y, et al. Tricuspid regurgitation and long-term clinical outcomes. Eur Heart J Cardiovasc Imaging. 2020;21(2):157-165. doi:10.1093/ehjci/jez216
(9) McKeown, LA. FDA Approves first Transcatheter Tricuspid Valve Replacement Device. TCTMD, February 2, 2024. Accessed: June 25, 2024. https://www.tctmd.com/news/fda-approves-first-transcatheter-tricuspid-valve-replacement-device
(10) Edwards EVOQUE Tricuspid Valve Replacement System Premarket Approval (PMA), Summary of Safety and Effectiveness. PMA: P230013. www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P230013
(11) Ambroggi M, Biasini C, Del Giovane C, Fornari F, Cavanna L. Distance as a Barrier to Cancer Diagnosis and Treatment: Review of the Literature. Oncologist. 2015 Dec;20(12):1378-85. doi: 10.1634/theoncologist.2015-0110. Epub 2015 Oct 28. PMID: 26512045; PMCID: PMC4679078.
(12) Nathan AS, Yang L, Yang N, et al. Racial, Ethnic, and Socioeconomic Disparities in Access to Transcatheter Aortic Valve Replacement Within Major Metropolitan Areas. JAMA Cardiol. 2022 February 1;7(2):150-157. doi: 10.1001/jamacardio.2021.4641. PMID: 34787635; PMCID: PMC8600460.
(13) Reddy KP, Groeneveld PW, Jay G, Fanaroff AC, Nathan AS. Economic Considerations in Access to Transcatheter Aortic Valve Replacement. Circ Cardiovasc Interv. 13 January 2022;15:e011489. doi.org/10.1161/CIRCINTERVENTIONS.121.011489
(14) Bevan GH, Zidar DA, Josephson RA, Al-Kindi SG. Mortality Due to Aortic Stenosis in the United States, 2008–2017. JAMA. 2019;321(22):2236–2238. doi:10.1001/jama.2019.6292.
(15) Sparrow RT, Sanjoy SS, Lindman BR, et al. Racial, Ethnic and Socioeconomic Disparities in Patients Undergoing Transcatheter Mitral Edge-to-Edge Repair. Int J Cardio. 2021 Dec 1;344:73–81. doi.org/10.1016/j.ijcard.2021.09.037
(16) Young, MN, Kearing S, Malenka D, Goodney PP, Skinner J, Iribarne A. Geographic and Demographic Variability in Transcatheter Aortic Valve Replacement Dispersion in the United States. J Am Heart Assoc. May 2021;10:e019588. doi.org/10.1161/JAHA.120.019588
(17) Kundi H, Faridi KF, Wang Y, et al. Geographic patterns of growth for transcatheter aortic valve replacement in the United States. Circulation. 2019;140(11):969–971. doi:10.1161/CIRCULATIONAHA.119.040788
(18) Bidwell J, Lyons K, Lee C. Caregiver well-being and patient outcomes in heart failure: A meta- analysis. J Cardiovasc Nurs. 2017; 32(4):372-382. doi:10.1097/JCN.0000000000000350
(19) Nishimura RA, O’Gara PT, Bavaria JE, Brindis RG, Carroll JD, Kavinsky CJ, Lindman BR, Linderbaum JA, Little SH, Mack MJ, Mauri L, Miranda WR, Shahian DM, Sundt TM III. 2019 AATS/ACC/ASE/SCAI/STS expert consensus systems of care document: a proposal to optimize care for patients with valvular heart disease: a joint report of the American Association for Thoracic Surgery, American College of Cardiology, American Society of Echocardiography, Society for Cardiovascular Angiography and Interventions, and The Society of Thoracic Surgeons. Ann Thorac Surg 2019 April 19
(20) Definitive Healthcare, 2023.
(21) Department of Health and human Services, Health Resources & Services Administration, Health Workforce Projections. Accessed: June 25, 2024. https://data.hrsa.gov/topics/health-workforce/workforce-projections
(22) Madhavan MV, Agarwal V, Hahn RT. Transcatheter Therapy for the Tricuspid Valve: A Focused Review of Edge-to-Edge Repair and Orthotopic Valve Replacement. Curr Cardiol Rep. 2024 Jun;26(6):459-474. doi: 10.1007/s11886-024-02051-4. Epub 2024 Jun 17. PMID: 38884853.
(23) Stolz, L., Kresoja, K.-P., von Stein, J., et al. (2024), Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry. Eur J Heart Fail. https://doi.org/10.1002/ejhf.3274
(24) Bugan B, Çekirdekçi EI, Onar LÇ, Barçin C. Transcatheter Tricuspid Valve Replacement for Tricuspid Regurgitation: A Systematic Review and Meta-analysis. Anatol J Cardiol. 2022 Jul;26(7):505-519. doi: 10.5152/AnatolJCardiol.2022.1440. PMID: 35791706; PMCID: PMC9318347.

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The tricuspid valve has been called the "forgotten valve" because few patients undergo isolated tricuspid valve surgery and those who do experience higher-than expected morbidity and mortality. Tricuspid regurgitation is often the result of years or decades of other heart disease, including left-sided valve disease, congestive heart failure, atrial fibrillation, or pacemaker implant. As our patient population ages, the prevalence of TR is increasing, and with increasing research we better understand the impact of TR on patients' functional status and quality of life. As surgery is not a good option for most patients, the availability of transcatheter technologies to treat TR allows us to improve patients' quality of life by performing a procedure that is safe, highly successful and that is associated with a very short recovery. We participated in the TRISCEND II study and treated about 10 patients who uniformly reported improvements in quality of life and functional status after therapy. I ask that CMS not only approve coverage for transcatheter tricuspid valve replacement procedures, but I ask that you rethink the reimbursement for strategies such as TAVR, MTEER, TTEER, TMVR and TTVR. Saint Luke's MAHI is one of the premier heart hospitals in the Midwest and we perform all of these procedures, but we are not reimbursed fairly. The reimbursement for all procedures is indexed to cost-of-living, which is a fair notion. But for the procedures listed, the (large) majority of the hospital cost is determined by the device cost, which is not any lower for MAHI than for hospitals in NY or CA for example. One solution is relatively simple - reimburse the device cost and index the remainder of the hospital reimbursement. This would better allow hospitals in our region to provide these important procedures for our patients and communities. Best, Adnan Chhatriwalla MD; Medical Director of Structural Intervention, Saint Luke's Mid America Heart Institute, Kansas City, MO

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Dear CMS,
This is an incredibly important and historical decision for patients with tricuspid valvular heart disease. These patients have minimally effective medicines (diuretics) and no Class 1 recommended invasive therapy. For the first time, Transcatheter Tricuspid Valve Replacement (TTVR) has shown such promising results and even a trend towards mortality benefit after 1 year. This has finally brought hope to millions of patients, their referring providers and treating physicians.
These patients have been massively underserved for decades and therefore it is important to ensure safe availability but at the same time not place unnecessary restrictions or barriers. Just like many other complex cardiac patients are evaluated in clinic by qualified physicians for multivessel CAD, heart valve surgery, these TR patients can easily and thoughtfully be evaluated by any single physician trained in Transcatheter Interventions. Mandating multiple physician evaluation is waste of resources, increases health care cost and most importantly delays and often completely limits access to care. Consult from other specialists like Heart Failure, Electrophysiology, Cardiac Surgery can always be obtained on a case by case basis as clinically indicated.
We have personal experience of evaluating and treating Evoque patients for several years as part of Early Feasibility Study (TRISCEND EFS) and then Randomized Control Trial (TRISCEND II) where we were one of the highest enrollers. Our patients have dramatically done well and some heve termed it "magical" and some "revolutionary". It is common for patients to ask “would you do on your family member” and the answer whole heartedly has been “yes, absolutely, any day”. While there are periprocedural events like conduction block, the actual intraprocedural complications are negligible and the procedure is fairly prescriptive these days (thanks to pre-procedural planning). Therefore, we must not overtly restrict this therapy. There are already 3 physicians in the room: an Echocardiographer (Imaging Cardiologist), an Anesthesiologist and an Implanter (Interventional Cardiologist or sometimes a Surgeon) working together with the help of company reps. We strongly feel Evoque TTVR is a single implanter procedure. There is no additional value/benefit in "mandating" multiple implanting physicians scrubbed at the same time, which rather once again carry the risk of limiting care (managing multiple schedules becomes challenging/nightmare) and most definitely waste of hospital resources (would rather have this second implanter take care of other patients).
We hope the potential of TTVR is fully realized and we do everything possible as a society to make it accessible to millions of anticipating patients.

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Dear Centers for Medicare & Medicaid Services,

I am writing to strongly advocate for the National Coverage Analysis (NCA) of the EVOQUE tricuspid valve replacement system. This revolutionary technology addresses a tremendous unmet need in the treatment of tricuspid regurgitation, a condition that has long challenged clinicians and significantly impacted patient quality of life.

The EVOQUE system represents a paradigm shift in tricuspid valve treatment. As an experienced operator who has performed over 100 research compassionate use cases using various transcatheter tricuspid therapies, including T-TEER, TTVR, and TricValve, I can attest to the transformative potential of this technology. Our results have been nothing short of amazing, demonstrating significant improvements in patient outcomes and quality of life.

It is crucial to emphasize that the success of this procedure relies heavily on the skill and experience of the operators. Proficiency in M-TEER (Mitral Transcatheter Edge-to-Edge Repair) is essential, as it provides the foundational skills necessary for tricuspid interventions. Furthermore, the procedure should be performed by a comprehensive heart team including a heart failure specialist, electrophysiologist, cardiac imager, and interventional surgeon. This multidisciplinary approach ensures optimal patient selection and procedural outcomes.

TTVR, in particular, has shown to be remarkably user-friendly and consistently delivers excellent results when patients are carefully selected. The reliability and reproducibility of these outcomes make it a game-changer in tricuspid valve treatment.

The available evidence, while still emerging, is extremely promising. Studies have shown significant reductions in tricuspid regurgitation, improvements in right ventricular function, and enhanced quality of life for patients. These results are particularly impressive given the historically poor outcomes and limited treatment options for tricuspid valve disease.

I strongly urge CMS to consider the following in their coverage determination:

- Recognize the revolutionary nature of this technology and its potential to dramatically improve outcomes for a traditionally underserved patient population.
- Ensure coverage is aligned with the approved label to allow for appropriate patient access.
- Implement operator and site volume requirements that reflect the necessary expertise while still allowing for equitable access.
- Require a multidisciplinary heart team approach to ensure optimal patient selection and care.
- Support ongoing evidence generation through coverage with evidence development (CED) to further refine and improve this groundbreaking therapy.

The EVOQUE system and similar transcatheter tricuspid therapies represent a beacon of hope for patients who previously had few, if any, viable treatment options. By providing coverage for this technology, Medicare can play a crucial role in advancing cardiovascular care and improving the lives of countless beneficiaries.

Thank you for your consideration of this vitally important matter.

Sincerely,

Jeremiah P. Depta, MD, MPHS, FACC, FSCAI
Director of the Advanced Valvular and Structural Heart Disease Program
Sands-Constellation Heart Institute
Rochester General Hospital

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