Artificial Hearts and related devices, including Ventricular Assist Devices for Bridge-to-Transplant and Destination Therapy

CMS NCA document | source_status=Closed | review_type=New | public_comment_open=False | document_id=CAG-00453N

A. The Centers for Medicare & Medicaid Services (CMS) is making changes to two separate, but medically related, National Coverage Determinations (NCDs). Given new evidence in the peer-reviewed medical literature, we are removing the NCD for Artificial Hearts and Related Devices established at §20.9 of the Medicare National Coverage Determination Manual. We are also revising the NCD at § 20.9.1 that provides coverage for Ventricular Assist Devices (VADs) for Bridge-to-Transplant and Destination Therapy. We summarize the changes below and fully explain the changes in the Analysis section of this NCD decision memo. Artificial Hearts CMS is removing the NCD at § 20.9, ending coverage with evidence development for artificial hearts and permitting Medicare coverage determinations for artificial hearts to be made by the Medicare Administrative Contractors (MACs) under § 1862(a)(1)(A) of the Social Security Act. Ventricular Assist Devices The decision is limited to durable, intracorporeal, left ventricular assist devices (LVADs), and does not include temporary VADs or extracorporeal membrane oxygen (ECMO). CMS is establishing coverage according to the following conditions: Patient Selection Criteria Removes the current therapeutic intent-to-treat criteria of bridge-to-transplant (BTT) and destination therapy (DT), by removing the following BTT requirements: The requirement that the patient is active on the waitlist maintained by the Organ Procurement and Transplantation Network (OPTN). The requirement that the implanting site, if different than the Medicare-approved transplant center, must receive written permission from the Medicare-approved transplant center prior to implantation of the VAD. Extends evidence based patient selection criteria, that previously applied only to DT, for all LVAD procedures for short-term (e.g., bridge-to-recovery and bridge-to-transplant) or long-term (e.g., destination therapy) mechanical circulatory support (see below in covered indications). Modifies patient selection criteria to reflect the major inclusion criteria of contemporary trials. Facility criteria The facility criteria remain unchanged from the current NCD. The removal of therapeutic intent is not expected to decrease appropriate patient access to LVADs. Below is the 20.9.1 NCD (Ventricular Assist Devices). All proposed changes are in italics. Any part of 20.9.1 that is not italicized is not proposed to be revised. B. Covered Indications 1. Advanced Heart Failure Left ventricular assist devices (LVADs) are covered if they are FDA approved for short-term (e.g., bridge-to-recovery and bridge-to-transplant) or long-term (e.g., destination therapy) mechanical circulatory support for heart failure patients who meet the following criteria: Have New York Heart Association (NYHA) Class IV heart failure; and Have a left ventricular ejection fraction (LVEF) ≤ 25%; and Are inotrope dependent OR have a Cardiac Index (CI) < 2.2 L/min/m2, while not on inotropes, and also meet one of the following: Are on optimal medical management (OMM), based on current heart failure practice guidelines for at least 45 out of the last 60 days and are failing to respond; or Have advanced heart failure for at least 14 days and are dependent on an intra‐aortic balloon pump (IABP) or similar temporary mechanical circulatory support for at least 7 days. Beneficiaries receiving a VAD must be managed by an explicitly identified, cohesive, multidisciplinary team of medical professionals with appropriate qualifications, training, and experience. The team embodies collaboration and dedication across medical specialties to offer optimal patient-centered care. Collectively, the team must ensure that patients and caregivers have the knowledge and support necessary to participate in informed decision making. The team members must be based at the facility and must include individuals with experience working with patients before and after placement of a VAD. The team must include, at a minimum: At least one physician with cardiothoracic surgery privileges and individual experience implanting at least 10 durable, intracorporeal, left ventricular assist devices over the course of the previous 36 months with activity in the last year. At least one cardiologist trained in advanced heart failure with clinical competence in medical- and device-based management including VADs, and clinical competence in the management of patients before and after placement of a VAD. A VAD program coordinator. A social worker. A palliative care specialist. The process for organizations to apply for CMS approval to be designated as a credentialing organization for VAD facilities is posted on our web site along with a list of approved credentialing organizations, approved standard versions, and credentialed facilities: http://www.cms.gov/Medicare/Medicare-General-Information/MedicareApprovedFacilitie/VAD-Destination-Therapy-Facilities.html See Appendix B for the manual language.

Decision Memo: Administrative File: CAG-00453N FROM: Tamara Syrek Jensen, JD Director, Coverage and Analysis Group Joseph Chin, MD, MS Deputy Director, Coverage and Analysis Group Steven A. Farmer, MD, PhD Chief Strategy Officer Melissa Evans, PhD, MSAE Director, Division of Policy and Evidence Review Lori Ashby, MA Deputy Director, Division of Policy and Evidence Review David Dolan, MBA Lead Analyst Rachel Katonak, PhD, RN Analyst Patricia Bright, PhD, MSPH, RN Lead Epidemiologist Joseph Dolph Hutter, MD, MA Lead Medical Officer SUBJECT: National Coverage Determinations for Artificial Hearts and related devices (§20.9) and Left Ventricular Assist Devices (§ 20.9.1) (CAG-00453N) DATE: December 1, 2020 I. Decision A. The Centers for Medicare & Medicaid Services (CMS) is making changes to two separate, but medically related, National Coverage Determinations (NCDs). Given new evidence in the peer-reviewed medical literature, we are removing the NCD for Artificial Hearts and Related Devices established at §20.9 of the Medicare National Coverage Determination Manual. We are also revising the NCD at § 20.9.1 that provides coverage for Ventricular Assist Devices (VADs) for Bridge-to-Transplant and Destination Therapy. We summarize the changes below and fully explain the changes in the Analysis section of this NCD decision memo. Artificial Hearts CMS is removing the NCD at § 20.9, ending coverage with evidence development for artificial hearts and permitting Medicare coverage determinations for artificial hearts to be made by the Medicare Administrative Contractors (MACs) under § 1862(a)(1)(A) of the Social Security Act. Ventricular Assist Devices The decision is limited to durable, intracorporeal, left ventricular assist devices (LVADs), and does not include temporary VADs or extracorporeal membrane oxygen (ECMO). CMS is establishing coverage according to the following conditions: Patient Selection Criteria Removes the current therapeutic intent-to-treat criteria of bridge-to-transplant (BTT) and destination therapy (DT), by removing the following BTT requirements: The requirement that the patient is active on the waitlist maintained by the Organ Procurement and Transplantation Network (OPTN). The requirement that the implanting site, if different than the Medicare-approved transplant center, must receive written permission from the Medicare-approved transplant center prior to implantation of the VAD. Extends evidence based patient selection criteria, that previously applied only to DT, for all LVAD procedures for short-term (e.g., bridge-to-recovery and bridge-to-transplant) or long-term (e.g., destination therapy) mechanical circulatory support (see below in covered indications). Modifies patient selection criteria to reflect the major inclusion criteria of contemporary trials. Facility criteria The facility criteria remain unchanged from the current NCD. The removal of therapeutic intent is not expected to decrease appropriate patient access to LVADs. Below is the 20.9.1 NCD (Ventricular Assist Devices). All proposed changes are in italics. Any part of 20.9.1 that is not italicized is not proposed to be revised. B. Covered Indications 1. Advanced Heart Failure Left ventricular assist devices (LVADs) are covered if they are FDA approved for short-term (e.g., bridge-to-recovery and bridge-to-transplant) or long-term (e.g., destination therapy) mechanical circulatory support for heart failure patients who meet the following criteria: Have New York Heart Association (NYHA) Class IV heart failure; and Have a left ventricular ejection fraction (LVEF) ≤ 25%; and Are inotrope dependent OR have a Cardiac Index (CI) < 2.2 L/min/m2, while not on inotropes, and also meet one of the following: Are on optimal medical management (OMM), based on current heart failure practice guidelines for at least 45 out of the last 60 days and are failing to respond; or Have advanced heart failure for at least 14 days and are dependent on an intra‐aortic balloon pump (IABP) or similar temporary mechanical circulatory support for at least 7 days. Beneficiaries receiving a VAD must be managed by an explicitly identified, cohesive, multidisciplinary team of medical professionals with appropriate qualifications, training, and experience. The team embodies collaboration and dedication across medical specialties to offer optimal patient-centered care. Collectively, the team must ensure that patients and caregivers have the knowledge and support necessary to participate in informed decision making. The team members must be based at the facility and must include individuals with experience working with patients before and after placement of a VAD. The team must include, at a minimum: At least one physician with cardiothoracic surgery privileges and individual experience implanting at least 10 durable, intracorporeal, left ventricular assist devices over the course of the previous 36 months with activity in the last year. At least one cardiologist trained in advanced heart failure with clinical competence in medical- and device-based management including VADs, and clinical competence in the management of patients before and after placement of a VAD. A VAD program coordinator. A social worker. A palliative care specialist. The process for organizations to apply for CMS approval to be designated as a credentialing organization for VAD facilities is posted on our web site along with a list of approved credentialing organizations, approved standard versions, and credentialed facilities: http://www.cms.gov/Medicare/Medicare-General-Information/MedicareApprovedFacilitie/VAD-Destination-Therapy-Facilities.html See Appendix B for the manual language. II. Background Throughout this document we use numerous acronyms, some of which are not defined as they are presented in direct quotations. Please find below a list of these acronyms and corresponding full terminology: 6-MWD – six-minute walk distance 6-MWT – six-minute walk test ACC – American College of Cardiology ACCF – American College of Cardiology Foundation ACE – Angiotensin-converting enzyme inhibitor ACGME - Accreditation Council for Graduate Medical Education ACP – American College of Physicians AHA – American Heart Association ARB – angiotensin receptor blocker BiVAD – biventricular assist device BMI – body mass index BSA – body surface area BTC – bridge to candidacy BTT – bridge to transplant CAP – continued access protocol CDC – Centers for Disease Control and Prevention CMS – Centers for Medicare & Medicaid Services CRT – Cardiac resynchronization therapy DNV – Det Norske Veritas Healthcare Inc. DT – destination therapy EQ-5D – EuroQuol-5D EQ-5D VAS – EuroQol-5D Visual Analog Scale FDA – Food and Drug Administration HFrEF – heart failure with reduced ejection fraction HFSA – Heart Failure Society of America HM II – HeartMate II Left Ventricular Assist System HM VE – HeartMate Vented Electric Left Ventricular Assist System HM XVE – HeartMate XVE HRQOL - health-related quality of life HRSA – Health Resources and Services Administration HW VAS – HeartWare Ventricular Assist System IABP – intraaortic balloon pump ICD – implantable cardioverter defibrillator INTERMACS – Interagency Registry for Mechanically Assisted Circulatory Support ISHLT - International Society for Heart and Lung Transplantation LVAD – left ventricular assist device LVEF – left ventricular ejection fraction KCCQ – Kansas City Cardiomyopathy Questionnaire KCCQ CSS – Kansas City Cardiomyopathy Questionnaire Clinical Summary Score KCCQ OSS – Kansas City Cardiomyopathy Questionnaire Overall Summary Score MAC - Medicare Administrative Contractor MCS – mechanical circulatory support MCSD – mechanical circulatory support device MEDCAC – Medicare Evidence Development and Coverage Advisory Committee METS – metabolic equivalent task score MLHFQ – Minnesota Living with Heart Failure Questionnaire NCA – National Coverage Analysis NCD – National Coverage Determination NHLBI – National Heart, Lung and Blood Institute NIH – National Institutes of Health NYHA – New York Heart Association OPTN – Organ Procurement and Transplantation Network PMA – premarket approval PROs – patient-reported outcomes QOL – quality of life REMATCH – Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure UNOS – United Network for Organ Sharing VAD – ventricular assist device Heart Failure Heart failure is a condition in which the heart cannot pump blood adequately to meet the body’s needs at rest or with exertion. About 6.5 million people in the United States have heart failure which is associated with significant mortality, morbidity, and healthcare expenditures, particularly among those aged ≥ 65 years old (CDC, 2019; Roger, 2013). In addition to age, which is an independent risk factor for heart failure, older adults often have additional risk factors such as high blood pressure, diabetes mellitus, coronary heart disease, tobacco use, and overweight/obesity and may have been exposed to these risk factors for many years. When the heart fails to adequately pump blood, excess fluid is retained and tissues do not get enough oxygen. This results in symptoms such as shortness of breath, swelling of the legs, and fatigue and causes substantial morbidity and, in the most serious circumstances, mortality. The leading cause of hospitalization among older adults is heart failure and Medicare beneficiaries with heart failure have the highest readmission rate of any condition (Jackson et al., 2018). Heart failure contributes to at least 287,000 deaths annually in the United States (Emory Healthcare, 2019). While there are objective measures of the severity of heart failure such as ejection fraction and cardiopulmonary exercise testing, care is most often driven by symptom-based classifications including the New York Heart Association (NYHA) Functional Classification, INTERMACS profiles, and the American Heart Association and American College of Cardiology (AHA/ACC) Stages of Heart Failure. NYHA Classification The NYHA Functional Classification is a subjective measure of the severity of heart failure symptoms which some have criticized as being unresponsive to change, having a high degree of interobserver variability, and providing the perspective of the doctor rather than the patient (Green, Porter, & Bresnahan, 2000; Miller & Guglin, 2013). The four NYHA classes include: Class I: Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea or anginal pain. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort increases. INTERMACS profiles were developed to further classify patients with advanced NYHA class III and class IV heart failure into one of seven profiles (Stevenson et al., 2009): Profile 1 - Critical cardiogenic shock: Patient with life-threatening hypotension despite rapidly escalating inotropic support, critical organ hypoperfusion, often confirmed by worsening acidosis and/or lactate levels. Profile 2 – Progressive decline: Patient with declining function despite intravenous inotropic support, may manifest with worsening renal function, nutritional depletion, or inability to restore volume balance. Also describes declining status in patients unable to tolerate inotropic therapy. Profile 3 - Stable but inotrope dependent: Patient with stable blood pressure, organ function, nutrition, and symptoms on continuous intravenous inotropic support (or a temporary circulatory support device or both), but demonstrating repeated failure to wean from support due to recurrent symptomatic hypotension or renal dysfunction. Profile 4 - Resting symptoms: Patient who can be stabilized close to normal volume status but experiences daily symptoms of congestion at rest or during activities of daily living. Doses of diuretics generally fluctuate at very high levels. Profile 5 - Exertion intolerant: Patient who is comfortable at rest and with activities of daily living but is unable to engage in any other activity, living predominantly within the house. Profile 6 - Exertion limited: Patient without evidence of fluid overload who is comfortable at rest, and with activities of daily living and minor activities outside the home but fatigues after the first few minutes of any meaningful activity. Profile 7 - Advanced NYHA class III: Patient who is clinically stable with a reasonable level of comfortable activity, usually able to walk more than a block. Has a history of previous decompensation but any decompensation requiring intravenous diuretics or hospitalization within the previous month should make this person a patient profile 6 or lower. The AHA/ACC Stages emphasize the development and progression of heart failure ranging from Stage A (risk factors but no current cardiac abnormality) to Stage D (refractory heart failure, may be eligible for advanced treatments such as continuous inotropes, heart transplant, ventricular assist device placement (VAD), or end-of-life care) (Yancy et al., 2017). Therapeutic interventions include modification of diet and lifestyle (such as restricting dietary sodium intake or increasing exercise) and medications including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), aldosterone antagonists, beta-blockers, or digoxin. In the most severe cases, intravenous inotropic medications can be used. Inotropic medications do not reverse heart failure but may improve symptoms by making the heart beat stronger or reducing strain on the heart by reducing blood pressure. Device therapies include implantable cardioverter defibrillators (ICDs) for patients at risk for sudden cardiac death; pacemakers and cardiac resynchronization devices for patients with abnormalities in the heart’s electrical conduction system; artificial hearts, and LVADs which are the subject of this analysis. Heart failure can be a progressive disease with increasing symptoms over time despite optimal medical management, though the time course is difficult to predict. Eventually, the heart fails completely and can no longer pump enough blood to sustain life. At this end-stage, eligible patients can undergo heart transplant; however, due to lack of available organs for transplant, many patients clinically decline or die on the transplant waitlist while awaiting life-saving transplantation (OPTN, 2019). In addition, older patients are often not eligible for heart transplant due to comorbid conditions, greatly increasing the risk of poor outcomes. Mechanical Circulatory Support There are a number of different mechanical devices that may be used to support the ventricles of a failing heart on either a temporary or a permanent basis. An artificial heart is an implanted prosthetic device that replaces the heart. Ventricular assist devices (VADs) or left ventricular assist devices (LVADs) are mechanical blood pumps that are surgically attached to one or both intact ventricles of a damaged or weakened native heart to assist in pumping blood. A relatively small proportion of patients suffer from biventricular failure. The artificial heart is a biventricular replacement device. Use of an artificial heart requires removal of both ventricles and removal of the device is not possible. In contrast, the heart remains intact with VADs with the possibility for the native heart to recover and for removal of the device. Patients who may be candidates for LVAD implant undergo extensive clinical testing to ensure an adequate severity of heart failure but acceptable severity of comorbidities. This evaluation attempts to balance the benefits that might be achieved by LVAD implant with the significant risks of the surgery and prolonged device support. Initially, LVADs were used in the hospital as short-term support for patients with acute heart failure caused by temporary conditions such as infection or open heart surgery. With the development of smaller implantable pumps, patients could be ambulatory, discharged from the hospital, and supported on device for longer periods of time. These durable LVADs were first introduced in patients on the heart transplant waitlist as a “bridge to transplant (BTT)” since the duration of support was intended to be finite. With heart transplants in limited supply and additional clinical experience gained, devices were subsequently implanted as “destination therapy (DT)” in patients who are ineligible for heart transplant who required permanent support. Heart failure patients that are candidates for LVAD therapy who are not classified as either BTT or DT at the time of LVAD implant are referred to as bridge to decision or bridge to candidacy (BTC). Some patients transition between the categories of BTT, BTC, and DT over time with the development or resolution of comorbid conditions. In addition, this categorization can be inconsistent due to differences in transplant approval and listing processes at individual transplant hospitals. The use of artificial hearts and related devices, including VADs, as a therapeutic tool has continued to evolve since our last national coverage analyses for BTT and DT. For VADs (NCD 20.9.1), the scope of this national coverage analysis (NCA) is limited to the coverage requirements for BTT and DT of durable LVADs for end-stage congestive heart failure. Specifically, we review the evidence for whether it supports changes to our current patient selection and facility criteria. III. History of Medicare Coverage Beginning in 1986, artificial hearts were non-covered under the Medicare program. In 2008, CMS began covering artificial hearts for bridge-to-transplant and destination therapy under coverage with evidence development for beneficiaries enrolled in a clinical study that meets all of the criteria specified in the NCD. In 1996, CMS began covering VADs implanted as BTT at Medicare-approved heart transplant centers. In 2001, CMS covered implantation at sites other than Medicare-approved heart transplant centers. Currently, devices are covered only if they have received approval from the FDA for that purpose, and the VADs are used according to FDA-approved labeling instructions. In 2003, CMS began covering VADs implanted as DT at Medicare-approved heart transplant centers meeting specific facility criteria including participation in a national, audited registry. In 2007, CMS allowed implantation at sites other than Medicare-approved heart transplant centers, named INTERMACS as the required registry, and required facilities to be credentialed by the Joint Commission based on standards dated February 2007. DT is for patients that require mechanical cardiac support. Currently, the VADs used for DT are covered only if they have received approval from the FDA for that purpose. The current patient selection criteria became effective November 9, 2010, and the current facility criteria became effective October 30, 2013. Since there are existing NCDs for artificial hearts and VADs, this review is a reconsideration of these current policies. The current policies are codified in sections 20.9 and 20.9.1 of the Medicare National Coverage Determinations manual. These sections of the NCD manual have been included in Appendix C and D. A. Current Request CMS received a complete, formal request from Syncardia to reconsider the coverage with evidence development (CED) requirement for artificial hearts for bridge-to-transplant based on new scientific evidence generated since the previous decision in 2008. Concurrently, CMS received a complete, formal request from Abbott Vascular asking that we reconsider the LVADs NCD to remove the therapeutic intent-to-treat criteria (e.g., bridge-to-transplant and destination therapy) for left ventricular assist device (LVAD) candidacy, and base LVAD coverage requirements on patient characteristics from new scientific evidence generated since the previous reconsideration of this NCD in 2013. The scope of this reconsideration is limited to the coverage requirements for LVADs for bridge-to-transplant and destination therapy. CMS is not reconsidering any other section of NCD 20.9.1. The formal request letters can be viewed via the tracking sheet for this NCA on the CMS website at https://www.cms.gov/medicare-coverage-database/details/nca-tracking-sheet.aspx?NCAId=298 . B. Benefit Category Medicare is a defined benefit program. For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in the Social Security Act. Artificial hearts qualify as: Inpatient Hospital Services Prosthetic Devices LVADs qualify as: Inpatient Hospital Services Note: This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service. IV. Timeline of Recent Activities Date Action February 3, 2020 CMS opens an NCA for Initial 30-day public comment period begins. March 4, 2020 First public comment period ends. CMS receives 35 comments. August 12, 2020 Proposed Decision Memorandum posted. 30-day public comment period begins. September 11, 2020 30-day public comment period ends. CMS receives 42 comments. V. Food and Drug Administration (FDA) Status The FDA approved the SynCardia Systems, Inc., CardioWest temporary Total Artificial Heart (hereinafter called the TAH-t) in 2004, which is indicated for use as a bridge to transplantation in cardiac transplant-eligible candidates at risk of imminent death from biventricular failure. The CardioWest TAH-t System is intended for use inside the hospital. The FDA has also approved several durable VADs for use as bridge-to-recovery (BTR), BTT, and/or DT in adults since 1992, some of which are pulsatile-flow pumps and are no longer in clinical use, such as the ABIOMED BVS 5000 Bi-Ventricular Support System (1992), Thoratec HeartMate IP (1994), Thoratec HeartMate VE (1998), and Thoratec HeartMate XVE (2001). Thoratec HeartMate II Left Ventricular Assist System (HM II) was the first continuous-flow blood pump, which received FDA approval for BTT in 2008 and for DT in 2010. The second continuous-flow blood pump approved by the FDA was the HeartWare HVAD, which was approved for BTT in 2012 and for DT in 2017. The latest continuous-flow blood pump approved by the FDA was the Thoratec HeartMate 3 Left Ventricular Assist System, which was first approved for providing short-term hemodynamic support (e.g., BTR or BTT) in 2017 and then for providing long-term hemodynamic support (e.g., DT) in 2018. All three of these VADs are in clinical use presently. VI. General Methodological Principles When making national coverage determinations, CMS generally evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within a benefit category is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. The critical appraisal of the evidence enables us to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for beneficiaries. An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary. A detailed account of the methodological principles of study design that the Agency utilizes to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix A. Public comments sometimes cite published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination. Public comments that contain personal health information will be redacted or will not be made available to the public. CMS responds in detail to the public comments on a proposed national coverage determination when issuing the final national coverage determination. VII. Evidence A. Discussion of Artificial Hearts Evidence 1. Artificial Hearts Evidence Question Q1: Is the evidence sufficient to end coverage with evidence development for artificial hearts? Artificial hearts are commonly referred to as total artificial hearts (TAH) due to there being only one device that is currently available on the market, which is the TAH-t. Data from patients receiving TAH are limited due to the extremely low volume of patients receiving such devices, as exemplified by the studies below: A peer-reviewed study conducted to inform CMS through coverage with evidence development (CED) identified 450 patients (87% men) who underwent a temporary TAH implantation as BTT or as BTD in the INTERMACS database between June 2006 and April 2017 (Arabia, 2018). Overall 3-,6-, and 12-month survival rates were 73%, 62%, and 53%, respectively. A 2016 study identified patients from the United Network of Organ Sharing database (a private, non-profit organization that manages U.S. organ transplants). They assessed patients aged > 18 years’ old who underwent heart transplantation between January 2005 and December 2014 comparing them to patients receiving biventricular assist device support as BTT (Cheng, 2016). The investigators identified 212 patients who received TAH with a mean age of 50 years (87% men). The 30-day, one-, and three-year post-transplantation survival was 88%, 78%, and 67%, respectively, for patients with TAH support. Investigators at the Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, studied 66 consecutive patients implanted with the TAH from 2006 through 2012 to assess outcomes by blinded, retrospectively adjudicated INTERMACS profiles (Shah, 2016). Survival after TAH implantation at 6 and 12 months was 76% and 71%, respectively. CMS did not request an external technology assessment (TA) and a MEDCAC meeting was not convened on this issue. B. LVADs Introduction The evidence summarized in this section includes the peer-reviewed, published clinical research pertinent to the use of durable, implantable left ventricular assist devices for advanced heart failure, whether for short-term use in patients who end up receiving an orthotopic heart transplant, or for long-term use in patients who never receive a transplant. Our assessment focuses exclusively on the two key questions below. 1. LVAD Evidence Question(s) Q1: Is the evidence sufficient to conclude that modifying the current patient selection criteria for LVAD implantation will improve health outcomes for Medicare beneficiaries? Q2: Is the evidence sufficient to conclude that modifying the current facility criteria for LVAD implantation will improve health outcomes for Medicare beneficiaries? 2. External Technology Assessments CMS did not request an external technology assessment (TA) on this issue. 3. Internal Technology Assessment Literature Search Methods CMS examined whether the evidence is adequate to support changes to our current patient selection or facility criteria for VADs. We included studies with publication dates on or after 2013 – February 2020. We searched the PubMed database and Cochrane library using the terms heart-assist device, heart assist pump, left ventricular assist device, LVAD, mechanical circulatory support, or INTERMACS; and bridge to transplant, bridge to candidacy, destination therapy, myocardial recovery, or heart transplantation. Additionally, we searched for guidelines and consensus statements relevant to our evidence questions. We limited our search to English language publications in humans over the age of 18. This search resulted in 985 publications, which we then reviewed by title and abstract to select papers potentially relevant to our evidence questions. We excluded studies of devices not currently approved by the FDA, devices that are no longer marketed, pre-pivotal studies of approved devices, studies of fewer than 50 VAD recipients, retrospective single-center case series, studies reporting only intermediate or surrogate outcomes, studies only reporting outcomes following heart transplant, or studies of cost or cost effectiveness. We also excluded studies focused only on pulsatile, temporary (non-durable), percutaneous, right-sided, biventricular, or partial-support devices and studies of artificial hearts. The clinical trials and observational studies that were relevant to our key questions and informed our decision language appear in the tables below. Table 1. Key LVAD Trials and Registry Studies – Advanced Heart Failure (Since the CMS 2013 NCD, with original reference trials in italics ) Study Design P I C O Results Year Study/Author Type Sites+ Size (N) Patients included Age (yrs) I;C Male (%) I;C Intervention Control Outcome (Primary) Based on Primary Outcome 2001 REMATCH (Rose) RCT (1:1) 20 US 129 DT (destination therapy; ineligible for heart transplant) NYHA class IV ≥ 90 days on OMT LVEF ≤ 25% Peak O2 consumption ≤ 12 ml per/kg/min; OR Inotrope dependent, decreasing renal function, or worsening pulmonary congestion 66; 68 78; 82 HeartMate 1 (pulsatile-flow) Medical Therapy Survival at 1 yr (overall) HM1 superior to medical therapy HM1 52% Medical 25% (P = 0.002) 2009 Heart Mate II (Slaughter) RCT (2:1) 38 US 200 ΔT 62; 63 81; 92 HeartMate II (axial-flow) HeartMate 1 (pulsatile-flow) Survival at 2 yrs free of disabling stroke and reoperation HMII superior to HM1 HMII 46% HM1 11% (P < 0.001) 2014 HeartMate II DT FDA Post-Approval (Jorde) Obser. 61 US Regis; 34 US RCT 380 DT 1 st 247 HMII DT patients in INTERMACS Registry v. 133 HMII DT patients in 2009 HMII RCT 70; 62 ( ≥ 60 yrs) 83; 80 Community implant of HeartMate II (Registry) Clinical trial implant of HeartMate II (RCT) Survival at 2 yrs free of disabling stroke and reoperation HMII in community superior or similar to HMII in trial Registry HMII 54% RCT HMII 44% (P = 0.042) 2015 INTERMACS Annual Rpt-7 th (Kirklin) Obser. 158 US 15,745 All devices Continuous-flow (CF): N=12,030 Intent (CF devices): 27% BTT (bridge to transplant; awaiting heart transplantation) listed, 38% T N/R N/R N/A N/A Survival at various yrs Survival (full cohort): 1 yr 80%; 2 yrs 70% Survival (DT, 2012-14): 1 yr 76%; 3 yrs 57% 2017 ENDURANCE (Rogers) RCT (2:1) 48 US 446 DT NYHA class IIIB* or IV LVEF ≤ 25% On OMM, including dietary salt restriction and diuretics, 45 of the last 60 days and failing to respond; OR Advanced HF for at least 14 days, and dependent on IABP for 7 days and/or inotropes for at least 14 days 63.9; 66.2 76.4; 82.4 HeartWare (centrifugal-flow) HeartMate II (axial-flow) Survival at 2 yrs free of disabling stroke and reoperation~ HW centrifugal noninferior HW 55.0% HMII 57.4% (P = 0.67) HW with more strokes HMII with more reoperations 2018 Euromacs 2 nd Rpt (de By) Obser. 52 Eur 2681 All devices Continuous-flow (CF), BTT or DT: N=2,113 51.7 82 N/A N/A Survival at various yrs Survival (CF LVAD, BTT or DT): 1 yr 69% 2 yrs 55% 3 yrs 44% BTT survival > DT 2019 MOMENTUM 3 (Mehra) RCT (1:1) 69 US 1028 DT, BTT, BTC (bridge to candidacy for transplant; not current transplant candidates but may become candidates for heart transplantation) NYHA class III with dyspnea upon mild physical activity, or NYHA class IV LVEF ≤ 25% Inotrope dependent; OR Not inotrope dependent, but CI <2.2 L/min/m 2 , and either: on OMM 45 of last 60 days and failing to respond; OR advanced HF for at least 14 days and dependent on IABP for at least 7 days 59; 60 79.7; 81.8 HeartMate 3 (centrifugal) HeartMate II (axial) Survival at 2 yrs free of disabling stroke and reoperation HM3 centrifugal superior to HMII axial (driven by reoperations) 2-yr results: HM3 76.9% HMII 64.8% (P < 0.001) 1-yr results: HM3 84% HMII 74.8%* HM3 with lower adverse event rates for stroke, bleeding, and pump thrombosis 2019 INTERMACS 2018 Annual Rpt (Kormos) Obser. Natl US 18,539 (2012-2017: 14,195) Isolated continuous-flow LVAD implanted (74% of total registry patients) Intent: 26% BTT, 43% DT LVAD: 78% axial, 22% centrifugal (1% HM3) 57.1 78.8 N/A N/A Survival at yrs 1 and 5 Results for 2012-2017 era: Survival (full cohort): 1 yr 83%; 5 yrs 46% Survival at 1 yr: Centrifugal 85% Axial 84% Survival at 5 yrs: Centrifugal 49% Axial 46% Survival (DT): 1 yr 80%; 3 yrs 59% Results from 2008-2017: Adverse events at 1 yr: Centrifugal (1% HM3) with more neuro events and pump-related infections. Axial with more GI bleeds 2020 MOMENTUM 3 Subgroup Analysis (Goldstein) RCT Sub-group 69 US 1028 (1:1) Secondary analysis of M3 trial: outcomes of LVAD use by BTT/BTC or DT therapy intent NYHA class III with dyspnea upon mild physical activity, or NYHA class IV LVEF ≤ 25% Inotropes as in M3 trial above 59; 60 79.7; 81.8 BTT/BTC patients (HM3 and HMII) DT patients (HM3 and HMII) Survival at 2 yrs free of disabling stroke and reoperation Superior effect on outcomes of HM3 over HMII was similar in BTT/BTC and T groups 2020 INTERMACS 2019 Annual Rpt (Teuteberg) Obser. Natl US 13,016 (2014-2018) Isolated continuous flow LVADs: 53% axial, 37% centrifugal, 10% HM3 Intent:52% DT, 46% BTT 'Control' = Baseline era 2014-16 ‘Intervention’ = Contemporary era 2017-2018 57.1; 57 77.3; 78.6 2017-18 data 2014-2016 data Survival at various yrs. Results for full cohort (2014-2018): Survival at 1 yr: 82% Survival at 5 yrs: 47% Overall survival and freedom from major adverse events higher with contemporary, centrifugal-flow full magnetic levitation devices (e.g., HM3). PICO is Population, Intervention, Control, Outcomes. I = intervention, C = Control. OMT = optimal medical therapy RCT = randomized controlled trial + All trials and studies are multicenter. ^ Disabling stroke is Rankin scale > 3 for all trials and studies. ~ Reoperation to remove or replace because of a failure of the original device Table 2. LVAD Studies on Facility/Volume Requirements (Since the CMS 2013 NCD) Study Design P I C O Results Year Study / Author Type Sites+ Size (N) Patients included Age (yrs) Male (%) Intervention Control Outcome (Primary) Based on Primary Outcome 2016 Academic Centers: Outcomes and Volume (Davis, Hohmann, Doukky, Levine, & Johnson) Obser. 88 US 7714 patients and 581 surgeons Academic Med Centers: any LVAD implant, DT or BTT Survived v died by procedure volume Surv;Died 56; 59 Surv;Died 78%; 75 N/A N/A In-hospital all-cause mortality Surgeons’ LVAD procedure volume, not annual hospital procedure volume, are assoc. with in-hospital mortality 2016 NIS: Outcomes and Volume (Shah) Obser. Natl US 1749 National Inpatient Sample: all LVAD outcomes by hospital volume tertiles 55.4 77 N/A N/A In-hospital all-cause mortality; length of stay (LOS) High annual LVAD volume assoc. with lower in-hospital mortality and LOS; optimal volume threshold: > 20 LVADs/yr 2017 INTERMACS: Outcomes and Volume (Cowger) Obser. Natl US 2012-2014: 7416 INTERMACS registry (2012-2014): all LVAD outcomes by hospital volume quartiles > 60 (49%) 79 N/A N/A 1 yr survival (overall) Results 2012-2014: Very low annual LVAD volume ( < 10/yr), and high volume ( > 50/yr) assoc. with lower survival, compared to midrange hospitals (31-50/yr) 2018 INTERMACS: Transplant Centers Better? (Brinkley) Obser. Natl US 3583 INTERMACS registry: outcomes at transplant centers (3323 patients) v non-transplant centers (260 patients) Isolated continuous-flow LVAD implanted for DT Cntr: Tr;NoTr 65; 65 Cntr: Tr;nonTr 81.3; 79.6 Non-transplant center Transplant center “Survival, censored at device explant for recovery or transplant” DT outcomes similar at transplant and non-transplant centers for: 30 day and 1 yr survival; death or major adverse events. Patients at transplant centers were sicker 4. Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) A MEDCAC meeting was not convened on this issue. 5. Evidence-Based Guidelines The pertinent evidence-based guidelines are summarized below (in order of most recent). Kirklin JK, Pagani FD, Goldstein DJ, et al. American Association for Thoracic Surgery/International Society for Heart and Lung Transplantation guidelines on selected topics in mechanical circulatory support (Guidelines) J Heart Lung Transplant. 2020 Mar; 39(3):187-219. This is the most recently published professional society guideline. The guideline covers a range of topics from preoperative evaluation through surgical approach and management and draws on multiple sources including results of the two interim reports of the MOMENTUM 3 trial. The guideline states that the, “Preoperative evaluation of a patient considered for implantation of a durable LVAD begins with assessment of the criteria that define the indication for implant (e.g., bridge to transplant [BTT], bridge to candidacy, or destination therapy [DT]).” As a general conclusion in the section on preoperative evaluation and optimization, the authors state, “Although individual organ system dysfunction may be an absolute contraindication for VAD surgery, a decision to implant will often involve a cumulative assessment of several relative contraindications and the associated overall risk.” The guideline notes that in the setting of a maximal study (respiratory exchange ratio > 1.1), peak oxygen consumption < 14 mL/kg/min (or < 50% of predicted, whichever is lowest), and/or a ventilation/carbon dioxide production slope > 36 have been associated with marked impairment in cardiac reserve and poor short- to intermediate-term prognosis. Most US payers use these values as qualifying criteria for destination therapy LVAD implantation. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. 28 Apr 2017 https://doi.org/10.1161/CIR.0000000000000509 Circulation. 2017;136:e137–e161. The 2013 guidelines, to which this is a 2017 focused update, was previously reviewed in our 2013 NCD. The update briefly addresses LVADs or MCS. Symptomatic patients with refractory NYHA class III-IV (stage D) should be considered for LVAD, transplant, or palliative care: FIGURE 1 Treatment of HFrEF Stage C and D (Yancy et al., 2017) For all medical therapies, dosing should be optimized and serial assessment exercised. *See text for important treatment directions. †Hydral-Nitrates green box: The combination of ISDN/HYD with ARNI has not been robustly tested. BP response should be carefully monitored. ‡See 2013 HF guideline(9). §Participation in investigational studies is also appropriate for stage C, NYHA class II and III HF. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor-blocker; ARNI, angiotensin receptor-neprilysin inhibitor; BP, blood pressure; bpm, beats per minute; C/I, contraindication; COR, Class of Recommendation; CrCl, creatinine clearance; CRT-D, cardiac resynchronization therapy–device; Dx, diagnosis; GDMT, guideline-directed management and therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter-defibrillator; ISDN/HYD, isosorbide dinitrate hydral-nitrates; Kþ, potassium; LBBB, left bundle-branch block; LVAD, left ventricular assistdevice; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSR, normal sinus rhythm; and NYHA, New York Heart Association. In a companion slide presentation of this focused update, the authors describe “Stage D Refractory [heart failure]” as “e.g., patients with: Marked [heart failure] symptoms at rest; Recurrent hospitalizations despite GDMT” [guideline directed management and therapy]. NICE. Implantation of a left ventricular assist device for destination therapy in people ineligible for heart transplantation. Interventional procedures guidance. Published: 27 March 2015 www.nice.org.uk/guidance/ipg516 . The NICE guidance is general, and emphasizes team care: 1 Recommendations 1.1 Current evidence on the efficacy and safety of the implantation of a left ventricular assist device for destination therapy in people ineligible for heart transplantation is adequate to support the use of this procedure provided that normal arrangements are in place for clinical governance, consent and audit. 1.2 Patient selection should be done by a multidisciplinary team that includes a cardiologist with a specialist interest in heart failure, a cardiothoracic surgeon and a cardiac anesthetist (see section 1.3). 1.3 Implantation of left ventricular assist devices for destination therapy should be done by surgeons, anesthetists and intensive care specialists with special training and regular practice in performing this procedure and caring for these patients. Subsequent care should be provided by a multidisciplinary team including staff with the expertise to deal with patients' medical and psychological management, and with the maintenance of their left ventricular assist devices. 6.1 The Committee noted that heart failure is very common. It considered that the use of left ventricular assist devices for destination therapy in people ineligible for heart transplantation needs very careful selection of patients who are likely to derive sustained benefit in terms of survival and quality of life. 6.2 The Committee recognized that this procedure is associated with a high incidence of complications, but it judged that the potential benefit for appropriately selected patients outweighed its potential for harm. 6.3 The Committee noted that technology for this procedure has evolved significantly in recent years and continues to do so. Note that the corresponding NICE guidance from 2006 for LVAD use for short-term circulatory support, at https://www.nice.org.uk/guidance/ipg177/chapter/2-The-procedure is very similar, also emphasizes team care, and adds these comments specific to short-term use: 2.5.1 This guidance refers to patients for whom other treatments such as intra-aortic balloon pumping would be ineffective, who are considered eligible for heart transplantation, or who have acute severe heart failure that is likely to be reversible (such as acute myocarditis). It was noted that other patients might potentially benefit from this procedure, such as patients who cannot be weaned off cardiopulmonary bypass after cardiac surgery and patients with cardiogenic shock after acute myocardial infarction. 6. Professional Society Recommendations / Consensus Statements / Other Expert Opinion (in order of most recent) Potapov EV, Antonides C, Crespo-Leiro MG, et al. 2019 EACTS Expert Consensus on long-term mechanical circulatory support. Eur J Cardiothorac Surg. 2019 Aug 1;56(2):230-270. doi: 10.1093/ejcts/ezz098. The European Association for Cardio-Thoracic Surgery (EACTS) state, “The evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field.” The authors provided the following background: “Long-term durable mechanical circulatory support (LT-MCS) has evolved significantly in the last decade. Today’s devices have become more reliable, and their durability has increased whereas device related complications have drastically decreased compared with earlier generations of devices.” They also support a change in terminology: “In this statement, we have generally refrained from using the designations of bridge to transplant and destination therapy in accordance with the more recent randomized trials in this field.” A central purpose of this expert consensus is to provide patient “selection criteria for evaluation of potential candidates.” As a summary of past (not the most recent) trials, they state that “Major trials have established the efficacy of LVADs in patients with a low left ventricular ejection fraction (< 25%), who were inotrope dependent or were persistently New York Heart Association (NYHA) functional class IIIb or IV despite optimal medical therapy. Additionally, a maximal oxygen consumption below 12 ml/kg/min was often used as an inclusion criterion.” The table below summarizes their current recommendations on specific patient characteristics. Table 3. EACTS Expert Consensus on long-term mechanical circulatory support Recommendation Class Level References It is recommended that reversible causes of heart failure are ruled out. I B LT-MCS implantation should be considered in patients with the following: New York Heart Association functional class IIIB–IV and Ejection fraction ≤ 25% and At least one of the following criteria: INTERMACS 2–4 Inotrope dependence Progressive end-organ dysfunction Peak VO2 < 12 ml/kg/min Temporary MCS dependence IIa B LT-MCS implantation should be considered in patients with the following: New York Heart Association functional class IIIB–IV and Ejection fraction ≤ 25% and At least one of the following criteria: INTERMACS 2–4 Inotrope dependence Progressive end-organ dysfunction Peak VO2 <12 ml/kg/min Temporary MCS dependence IIa B Patient characteristics associated with a high risk of poor outcome post-left ventricular assist device LT-MCS in patients with advanced age, after careful evaluation of comorbidities and frailty, should be considered. IIa C [3, 22-25] LT-MCS in patients with peripheral vascular disease, depending on its severity, may be considered. IIb C LT-MCS in patients with active systemic bacterial/fungal infection is not recommended. III B [26,27] In patients with well controlled HIV, hepatitis B or hepatitis C, LT-MCS should be considered. IIa B [26,27] In patients with diabetes with poor glycaemic control or end-organ complications, LT-MCS may still be considered. IIb B [22, 28-30] LT-MCS may be considered in patients with chronic dialysis. IIb C [31-34] LT-MCS implantation in patients with haemostatic deficiencies and coagulopathies may be considered. IIb B [35-38] LT-MCS implantation in patients with untreated aortic regurgitation or mechanical aortic valve is not recommended. III C [39,40] LT-MCS in patients with untreated severe mitral stenosis is not recommended. III C LT-MCS implantation in patients with irreversible liver dysfunction, as diagnosed by liver enzyme laboratory tests and the Model of End-stage Liver Disease score, is generally not recommended. III B [41] In patients with poor neurological and cognitive function, LT-MCS implantation is not recommended. III B [42,43] Frail patients and patients with limited mobility may, after careful evaluation, be considered for LT-MCS implantation. IIb B [44-48] LT-MCS in patients who are living alone or who are suffering from depression should, after careful evaluation, be considered. IIa C [19, 49-53] LT-MCS implantation in patients who suffer from dementia is not recommended. III C [19, 49-53] LT-MCS implantation in patients with active substance abuse, not willing to cease the abuse, is not recommended. III C LT-MCS implantation in patients with malignancies may be considered if expected survival is > 1 year. III C HIV: human immunodeficiency virus; INTERMACS: Interagency Registry for Mechanically Assisted Circulatory Support; LT-MCS: long-term mechanical circulatory support. Cook JL, Colvin M, Francis GS, et al. Recommendations for the Use of Mechanical Circulatory Support: Ambulatory and Community Patient Care: A Scientific Statement From the American Heart Association. Circulation. 2017 Jun 20;135(25):e1145-e1158. doi: 10.1161/CIR.0000000000000507. Epub 2017 May 30. Intended as recommendations to frontline community practitioners and first responders, the table on “Indications and Contraindications to Durable Mechanical Support” is relevant to this NCD. The criteria derive from past clinical guidelines and regulatory requirements (including the CMS 2013 NCD). Table 4. Indications and Contraindications to Durable Mechanical Support Indications: combination of the following: Frequent hospitalizations for heart failure NYHA class IIIb–IV functional limitations despite maximal therapy Intolerance of neurohormonal antagonists Increasing diuretic requirement Symptomatic despite CRT Inotrope dependence Low peak V O2 ( < 14–16) End-organ dysfunction attributable to low cardiac output Contraindications Absolute Irreversible hepatic disease Irreversible renal disease Irreversible neurological disease Medical non-adherence Severe psychosocial limitations Relative Age > 80 y for DT Obesity or malnutrition Musculoskeletal disease that impairs rehabilitation Active systemic infection or prolonged intubation Untreated malignancy Severe PVD Active substance abuse Impaired cognitive function Unmanaged psychiatric disorder Lack of social support ____________________________________________________________ CRT indicates cardiac resynchronization therapy; DT, destination therapy; NYHA, New York Heart Association; V O2 , oxygen consumption; and PVD, peripheral vascular disease. 7. Public Comment Public comments sometimes cite the published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous an