Transcatheter Edge-to-Edge Repair for Tricuspid Valve Regurgitation (T-TEER)

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A. Decision The Centers for Medicare & Medicaid Services (CMS) covers tricuspid transcatheter edge-to-edge repair (T-TEER) for the treatment of symptomatic tricuspid regurgitation (TR) under Coverage with Evidence Development (CED) according to the provisions in sections I.B. and I.C. below. B. Coverage Criteria T-TEER is covered when furnished according to a Food and Drug Administration (FDA) market-authorized indication and all the following conditions are met: 1. Patient Criteria Despite optimal medical therapy (OMT), patients must have symptomatic TR with tricuspid valve repair being considered as appropriate by a heart team. 2. Physician Criteria The patient (preoperatively and postoperatively) is under the care of a heart team, which includes, at minimum, the following: a) Cardiac surgeon; b) Interventional cardiologist; c) Cardiologist with training and experience in heart failure management; and d) Interventional echocardiographer. All the specialists listed above must have experience in the care and treatment of tricuspid regurgitation. 3. CED Study Criteria The T-TEER items and services are furnished in the context of a CMS-approved CED study. CMS-approved CED study protocols must: include only those patients who meet the criteria in section I.B.1; furnish items and services only through practitioners who meet the criteria in section I.B.2; and include all of the following: a) Primary outcomes of all-cause mortality, hospitalizations, or a composite of these, through a minimum of 24 months. For composite outcome measures, physiologic, patient-reported, and other relevant health outcomes should be co-directional (i.e., all outcomes comprising the composite outcome should demonstrate movement in the same direction). Each component of a composite outcome must be individually reported. b) An active comparator. c) A care management plan that includes the experience and role of each member of the heart team described in section I.B.2. d) Design sufficient for subgroup analyses by: Practitioner and facility level variables that predict the primary outcomes of the study; Clinically important patient demographic factors; Left ventricular ejection fraction (by guideline-defined subgroups); Previous tricuspid surgery or intervention; Severe aortic or mitral stenosis or regurgitation; Patients with chronic kidney disease; Patients with indwelling cardiac implantable electronic devices; Patients with greater than mild right ventricular dysfunction; Patients with hepatic dysfunction; and Grade of post-repair residual TR. e) CMS-approved CED studies must adhere to the following scientific standards (criteria 1-17 below) that have been identified by the Agency for Healthcare Research and Quality (AHRQ) as set forth in Section VI of CMS’ Coverage with Evidence Development Guidance Document , published August 7, 2024 (the “CED Guidance Document”). Sponsor/Investigator: The study is conducted by sponsors/investigators with the resources and skills to complete it successfully. Milestones: A written plan is in place that describes a detailed schedule for completion of key study milestones, including study initiation, enrollment progress, interim results reporting, and results reporting, to ensure timely completion of the CED process. Study Protocol: The CED study is registered with ClinicalTrials.gov and a complete final protocol, including the statistical analysis plan, is delivered to CMS prior to study initiation. The published protocol includes sufficient detail to allow a judgment of whether the study is fit-for-purpose and whether reasonable efforts will be taken to minimize the risk of bias. Any changes to approved study protocols should be explained and publicly reported. Study Context: The rationale for the study is supported by scientific evidence and study results are expected to fill the specified CMS-identified evidence deficiency and provide evidence sufficient to assess health outcomes. Study Design: The study design is selected to safely and efficiently generate valid evidence of health outcomes. The sponsors/investigators minimize the impact of confounding and biases on inferences through rigorous design and appropriate statistical techniques. If a contemporaneous comparison group is not included, this choice should be justified, and the sponsors/investigators discuss in detail how the design contributes useful information on issues such as durability or adverse event frequency that are not clearly answered in comparative studies. Study Population: The study population reflects the demographic and clinical diversity among the Medicare beneficiaries who are the intended population of the intervention, particularly when there is good clinical or scientific reason to expect that the results observed in premarket studies might not be observed in older adults or subpopulations identified by other clinical or demographic factors. Subgroup Analyses: The study protocol explicitly discusses beneficiary subpopulations affected by the item or service under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion requirements effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial. In the protocol, the sponsors/investigators describe plans for analyzing demographic subpopulations as well as clinically-relevant subgroups as identified in existing evidence. Description of plans for exploratory analyses, as relevant subgroups emerge, are also included. Care Setting: When feasible and appropriate for answering the CED question, data for the study should come from beneficiaries in their expected sites of care. Health Outcomes: The primary health outcome(s) for the study are those important to patients and their caregivers and that are clinically meaningful. A validated surrogate outcome that reliably predicts these outcomes may be appropriate for some questions. Generally, when study sponsors propose using surrogate endpoints to measure outcomes, they should cite validation studies published in peer-reviewed journals to provide a rationale for assuming these endpoints predict the health outcomes of interest. The cited validation studies should be longitudinal and demonstrate a statistical association between the surrogate endpoint and the health outcomes it is thought to predict. Objective Success Criteria: In consultation with CMS and AHRQ, sponsors/investigators establish an evidentiary threshold for the primary health outcome(s) so as to demonstrate clinically meaningful differences with sufficient precision. Data Quality: The data are generated or selected with attention to provenance, bias, completeness, accuracy, sufficiency of duration of observation to demonstrate durability of health outcomes, and sufficiency of sample size as required by the question. Construct Validity: Sponsors/investigators provide information about the validity of drawing warranted conclusions about the study population, primary exposure(s) (intervention, control), health outcome measures, and core covariates when using either primary data collected for the study about individuals or proxies of the variables of interest, or existing (secondary) data about individuals or proxies of the variables of interest. Sensitivity Analyses: Sponsors/investigators will demonstrate robustness of results by conducting pre-specified sensitivity testing using alternative variable or model specifications as appropriate. Reporting: Final results are provided to CMS and submitted for publication or reported in a publicly accessible manner within 12 months of the study’s primary completion date. Wherever possible, the study is submitted for peer review with the goal of publication using a reporting guideline appropriate for the study design and structured to enable replication. If peer-reviewed publication is not possible, results may also be published in an online publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTrials.gov, or in journals willing to publish in abbreviated format (e.g., for studies with incomplete results). Sharing: The sponsors/investigators commit to making study data publicly available by sharing data, methods, analytic code, and analytical output with CMS or with a CMS-approved third party. The study should comply with all applicable laws regarding subject privacy, including 45 CFR § 164.514 within the regulations promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient Records. Governance: The protocol describes the information governance and data security provisions that have been established to satisfy Federal security regulations issued pursuant to HIPAA and codified at 45 CFR Parts 160 and 164 (Subparts A & C), United States Department of Health and Human Services (HHS) regulations at 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient and HHS regulations at 45 CFR Part 46, regarding informed consent for clinical study involving human subjects. In addition to the requirements under 42 CFR and 45 CFR, studies that are subject to FDA regulation must also comply with regulations at 21 CFR Parts 50 and 56 regarding the protection of human subjects and institutional review boards, respectively. Legal: The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals, although it is acceptable for a study to test a reduction in toxicity of a product relative to standard of care or an appropriate comparator. For studies that involve researching the safety and effectiveness of new drugs and biological products aimed at treating life-threatening or severely-debilitating diseases, refer to additional requirements set forth in 21 CFR § 312.81(a). Consistent with section 1142 of the Act, AHRQ supports clinical researc

Decision Memo: DATE : July 2, 2025 Table of Contents Decision Decision Coverage Criteria Patient Criteria Physician Criteria CED Study Criteria Other Uses of T-TEER Clinical Review Background Food and Drug Administration Status Evidence Evidence Questions Technology Assessments Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) Clinical Literature Search Summary of Evidence Assessment of the Evidence Trial Design and Enrollment Criteria Study Populations Background Therapy Intervention Setting Endpoints RCT Study Quality and Risk of Bias Synthesizing the Clinical Trial Evidence Evidence from observational studies and relevance to Medicare beneficiaries Limitations of Evidence Considerations for Further Research Evidence-Based Guidelines Professional Society Recommendations / Consensus Statements / Other Expert Opinion Appropriate Use Criteria Public Comment Support for Medicare Coverage for T-TEER Non-Coverage for T-TEER Coverage Indications Physician Criteria Institutional Criteria Volume Criteria CED Criteria for T-TEER Miscellaneous Comments CMS Coverage Analysis CMS Coverage Authority CMS Analysis for Coverage of T-TEER for TR Rationale for Coverage Requirements for T-TEER for TR (Patient, Physician, and CED Study Criteria) Evidence Questions – Answered Benefit Category Shared Decision-Making History of Medicare Coverage Current National Coverage Request Timeline of NCA Milestones Appendices Appendix A: Medicare National Coverage Determinations Manual Language Appendix B: Referenced Materials Appendix C: Heart Failure Quality of Life and Functional Measures Abbreviations used throughout the Decision Memorandum for Transcatheter Edge-to-Edge Repair for Tricuspid Valve Regurgitation (T-TEER) 6MWD – Six-Minute Walk Distance 6MWT – Six-Minute Walk Test ACC – American College of Cardiology ADL – Activities of Daily Living AE – Adverse Event AF – Atrial Fibrillation AHA – American Heart Association AHRQ – Agency for Healthcare Research and Quality AS – Aortic Stenosis ASTR – Atrial Secondary Tricuspid Regurgitation BL – Baseline BNP – B-type natriuretic peptide CABG – Coronary Artery Bypass Graft CAD – Coronary Artery Disease CED – Coverage with Evidence Development CFR – Code of Federal Regulations CI – Confidence Interval CIED – Cardiac Implantable Electronic Device CMS – Centers for Medicare & Medicaid Services COPD – Chronic Obstructive Pulmonary Disease CT – Computed Tomography CV – Cardiovascular DVT – Deep Vein Thrombosis EACTS – European Association for Cardio-Thoracic Surgery EAPCI – European Association of Percutaneous Cardiovascular Interventions EP – Electrophysiologist EROA – Effective Regurgitant Orifice Area ESC – European Society of Cardiology EuroSCORE II – European System for Cardiac Operative Risk Evaluation II FAC – Fractional Area Change FDA – Food and Drug Administration GDMT – Guideline-Directed Medical Therapy HF – Heart Failure HFA – Heart Failure Association HR – Hazard Ratio ICD – Implantable Cardioverter Defibrillator IDE – Investigational Device Exemption IQR – Interquartile Range ITT – Intention-to-Treat IVC – Inferior Vena Cava KCCQ – Kansas City Cardiomyopathy Questionnaire LVEF – Left Ventricular Ejection Fraction MAC – Medicare Administrative Contractor MAE – Major Adverse Event MCID – Minimal Clinically Important Difference MEDCAC – Medicare Evidence Development & Coverage Advisory Committee MI – Myocardial Infarction MLHFQ – Minnesota Living with Heart Failure Questionnaire MR – Mitral Regurgitation M-TEER – Mitral Transcatheter Edge-To-Edge Repair NCA – National Coverage Analysis NCD – National Coverage Determination NYHA – New York Heart Association OMT – Optimal Medical Therapy OR – Odds Ratio PA – Pulmonary Artery PAP – Pulmonary Artery Pressure PASP – Pulmonary Artery Systolic Pressure PCI – Percutaneous Coronary Intervention PE – Pulmonary Embolism PH – Pulmonary Hypertension PM – Pacemaker PMA – Premarket Approval PPM – Permanent Pacemaker PH – Pulmonary Hypertension QoL – Quality of Life RA – Right Atrium RCT – Randomized Controlled Trial/Clinical Trial RHC – Right Heart Catheterization RHF – Right Heart Failure RVCPi – Right Ventricular Cardiac Power Index RV – Right Ventricle/Ventricular RVEDD – Right Ventricular End Diastolic Diameter RVFAC – Right Ventricular Fractional Area Change SCAI – Society for Cardiovascular Angiography and Interventions SD – Standard Deviation SDM – Shared Decision-Making SF-36 – Short Form Health Survey STS – Society of Thoracic Surgeons SPAP – Systolic Pulmonary Artery Pressure SSED – Summary of Safety and Effectiveness Data TAPSE – Tricuspid Annular Plane Systolic Excursion TAVR – Transcatheter Aortic Valve Replacement TCET – Transitional Coverage for Emerging Technologies TEE – Transesophageal Echocardiography TEER – Transcatheter Edge-To-Edge Repair TTE – Transthoracic Echocardiography T-TEER – Tricuspid Transcatheter Edge-to-Edge Repair TR – Tricuspid Regurgitation TV – Tricuspid Valve US – United States USPSTF – United States Preventive Services Task Force VHD – Valvular Heart Disease VSTR – Ventricular Secondary Tricuspid Regurgitation WR – Win Ratio I. Decision A. Decision The Centers for Medicare & Medicaid Services (CMS) covers tricuspid transcatheter edge-to-edge repair (T-TEER) for the treatment of symptomatic tricuspid regurgitation (TR) under Coverage with Evidence Development (CED) according to the provisions in sections I.B. and I.C. below. B. Coverage Criteria T-TEER is covered when furnished according to a Food and Drug Administration (FDA) market-authorized indication and all the following conditions are met: 1. Patient Criteria Despite optimal medical therapy (OMT), patients must have symptomatic TR with tricuspid valve repair being considered as appropriate by a heart team. 2. Physician Criteria The patient (preoperatively and postoperatively) is under the care of a heart team, which includes, at minimum, the following: a) Cardiac surgeon; b) Interventional cardiologist; c) Cardiologist with training and experience in heart failure management; and d) Interventional echocardiographer. All the specialists listed above must have experience in the care and treatment of tricuspid regurgitation. 3. CED Study Criteria The T-TEER items and services are furnished in the context of a CMS-approved CED study. CMS-approved CED study protocols must: include only those patients who meet the criteria in section I.B.1; furnish items and services only through practitioners who meet the criteria in section I.B.2; and include all of the following: a) Primary outcomes of all-cause mortality, hospitalizations, or a composite of these, through a minimum of 24 months. For composite outcome measures, physiologic, patient-reported, and other relevant health outcomes should be co-directional (i.e., all outcomes comprising the composite outcome should demonstrate movement in the same direction). Each component of a composite outcome must be individually reported. b) An active comparator. c) A care management plan that includes the experience and role of each member of the heart team described in section I.B.2. d) Design sufficient for subgroup analyses by: Practitioner and facility level variables that predict the primary outcomes of the study; Clinically important patient demographic factors; Left ventricular ejection fraction (by guideline-defined subgroups); Previous tricuspid surgery or intervention; Severe aortic or mitral stenosis or regurgitation; Patients with chronic kidney disease; Patients with indwelling cardiac implantable electronic devices; Patients with greater than mild right ventricular dysfunction; Patients with hepatic dysfunction; and Grade of post-repair residual TR. e) CMS-approved CED studies must adhere to the following scientific standards (criteria 1-17 below) that have been identified by the Agency for Healthcare Research and Quality (AHRQ) as set forth in Section VI of CMS’ Coverage with Evidence Development Guidance Document , published August 7, 2024 (the “CED Guidance Document”). Sponsor/Investigator: The study is conducted by sponsors/investigators with the resources and skills to complete it successfully. Milestones: A written plan is in place that describes a detailed schedule for completion of key study milestones, including study initiation, enrollment progress, interim results reporting, and results reporting, to ensure timely completion of the CED process. Study Protocol: The CED study is registered with ClinicalTrials.gov and a complete final protocol, including the statistical analysis plan, is delivered to CMS prior to study initiation. The published protocol includes sufficient detail to allow a judgment of whether the study is fit-for-purpose and whether reasonable efforts will be taken to minimize the risk of bias. Any changes to approved study protocols should be explained and publicly reported. Study Context: The rationale for the study is supported by scientific evidence and study results are expected to fill the specified CMS-identified evidence deficiency and provide evidence sufficient to assess health outcomes. Study Design: The study design is selected to safely and efficiently generate valid evidence of health outcomes. The sponsors/investigators minimize the impact of confounding and biases on inferences through rigorous design and appropriate statistical techniques. If a contemporaneous comparison group is not included, this choice should be justified, and the sponsors/investigators discuss in detail how the design contributes useful information on issues such as durability or adverse event frequency that are not clearly answered in comparative studies. Study Population: The study population reflects the demographic and clinical diversity among the Medicare beneficiaries who are the intended population of the intervention, particularly when there is good clinical or scientific reason to expect that the results observed in premarket studies might not be observed in older adults or subpopulations identified by other clinical or demographic factors. Subgroup Analyses: The study protocol explicitly discusses beneficiary subpopulations affected by the item or service under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion requirements effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial. In the protocol, the sponsors/investigators describe plans for analyzing demographic subpopulations as well as clinically-relevant subgroups as identified in existing evidence. Description of plans for exploratory analyses, as relevant subgroups emerge, are also included. Care Setting: When feasible and appropriate for answering the CED question, data for the study should come from beneficiaries in their expected sites of care. Health Outcomes: The primary health outcome(s) for the study are those important to patients and their caregivers and that are clinically meaningful. A validated surrogate outcome that reliably predicts these outcomes may be appropriate for some questions. Generally, when study sponsors propose using surrogate endpoints to measure outcomes, they should cite validation studies published in peer-reviewed journals to provide a rationale for assuming these endpoints predict the health outcomes of interest. The cited validation studies should be longitudinal and demonstrate a statistical association between the surrogate endpoint and the health outcomes it is thought to predict. Objective Success Criteria: In consultation with CMS and AHRQ, sponsors/investigators establish an evidentiary threshold for the primary health outcome(s) so as to demonstrate clinically meaningful differences with sufficient precision. Data Quality: The data are generated or selected with attention to provenance, bias, completeness, accuracy, sufficiency of duration of observation to demonstrate durability of health outcomes, and sufficiency of sample size as required by the question. Construct Validity: Sponsors/investigators provide information about the validity of drawing warranted conclusions about the study population, primary exposure(s) (intervention, control), health outcome measures, and core covariates when using either primary data collected for the study about individuals or proxies of the variables of interest, or existing (secondary) data about individuals or proxies of the variables of interest. Sensitivity Analyses: Sponsors/investigators will demonstrate robustness of results by conducting pre-specified sensitivity testing using alternative variable or model specifications as appropriate. Reporting: Final results are provided to CMS and submitted for publication or reported in a publicly accessible manner within 12 months of the study’s primary completion date. Wherever possible, the study is submitted for peer review with the goal of publication using a reporting guideline appropriate for the study design and structured to enable replication. If peer-reviewed publication is not possible, results may also be published in an online publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTrials.gov, or in journals willing to publish in abbreviated format (e.g., for studies with incomplete results). Sharing: The sponsors/investigators commit to making study data publicly available by sharing data, methods, analytic code, and analytical output with CMS or with a CMS-approved third party. The study should comply with all applicable laws regarding subject privacy, including 45 CFR § 164.514 within the regulations promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient Records. Governance: The protocol describes the information governance and data security provisions that have been established to satisfy Federal security regulations issued pursuant to HIPAA and codified at 45 CFR Parts 160 and 164 (Subparts A & C), United States Department of Health and Human Services (HHS) regulations at 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient and HHS regulations at 45 CFR Part 46, regarding informed consent for clinical study involving human subjects. In addition to the requirements under 42 CFR and 45 CFR, studies that are subject to FDA regulation must also comply with regulations at 21 CFR Parts 50 and 56 regarding the protection of human subjects and institutional review boards, respectively. Legal: The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals, although it is acceptable for a study to test a reduction in toxicity of a product relative to standard of care or an appropriate comparator. For studies that involve researching the safety and effectiveness of new drugs and biological products aimed at treating life-threatening or severely-debilitating diseases, refer to additional requirements set forth in 21 CFR § 312.81(a). Consistent with section 1142 of the Act, AHRQ supports clinical research studies that CMS determines meet all the criteria and standards identified above. C. Other Uses of T-TEER 1) Tricuspid transcatheter edge-to-edge repair (T-TEER) is not covered for patients outside of a CMS-approved study. 2) Nothing in this NCD would preclude coverage of T-TEER through NCD 310.1 (Clinical Trial Policy) or through the Investigational Device Exemption (IDE) Policy. See Appendix A for Medicare National Coverage Determinations Manual language. II. Clinical Review A. Background Etiology and Clinical Presentation: Tricuspid regurgitation (TR) is a cardiac condition that occurs when the tricuspid valve (TV) between the right atrium (RA) and right ventricle (RV) does not function properly, allowing blood to flow backwards from the RV to the RA. TR is typically classified as either primary or secondary based on its etiology. Primary, or degenerative, TR results from an intrinsic valve or sub-valvular abnormality, commonly originating from Ebstein anomaly, rheumatic valve disease, chest wall trauma, or complications from implantable device leads. Secondary TR, also called functional TR, is commonly caused by RV and RA dilatation with tricuspid annulus dilation and/or leaflet tethering from remodeling due to pulmonary hypertension, atrial fibrillation (AF), or other conditions that cause elevation in RV systolic pressure or RV dilation. Contemporary recommendations for classification further subdivide primary and secondary TR by etiology, as outcomes differ for different pathophysiologic etiologies (Hahn et al., 2023). It is notable that TR severity can change with changes in volume status and pulmonary pressure (Otto et al., 2021). Most adults in the general population experience at least trivial degrees of TR and most are asymptomatic, even in the presence of severe TR (Otto et al., 2021). When present, symptoms are those of right heart failure (HF), including peripheral edema, ascites, and painful hepatosplenomegaly. Sequelae include congestive hepatopathy with liver failure and renal impairment due to venous hypertension. Symptoms can include those of left-sided HF, such as shortness of breath, fatigue, weakness, and exercise intolerance, when this is the underlying etiology of TR. Epidemiology: An estimated 1.6 million individuals in the United States have moderate or greater TR (Cahill et al., 2021) and prevalence increases with age (Hahn, 2023). Approximately 80-95% of TR is secondary (Condello et al., 2021; Prihadi et al., 2019, Wang et al., 2022). TR is more frequent in women than men and female sex predicts greater severity of disease (Hahn, 2023). An analysis of the Framingham data (Singh et al., 1999) indicated that risk factors for TR were age (OR 1.5/9.9 years), body mass index (OR 0.7/4.3 kg/m 2 ), and female (OR 1.2). Other risk factors include atrial fibrillation, pulmonary hypertension, and left atrial enlargement (Hahn, 2023) and at least moderate TR develops in about 50% of individuals with severe mitral regurgitation (MR) and 25% of those with severe aortic stenosis (AS) (Condello et al., 2021), with risk persisting following repair. Diagnosis and Assessment: According to the 2020 American College of Cardiology/American Heart Association valve guidelines, transthoracic echocardiography (TTE) is currently the standard for TR diagnosis and severity assessment (Otto et al., 2021). TEE can be considered when TTE images are suboptimal or in specific cases such as endocarditis or the presence of pacemaker leads. The current American Society of Echocardiography parameters for grading the severity of chronic TR (mild, moderate, severe) include TV morphology, RV and right atrial (RA) size, inferior vena cava diameter, color flow jet area, flow convergence zone, hepatic vein flow, and effective regurgitant orifice area (Zoghbi et al., 2017). To better characterize the variability of TR seen in patients considered for transcatheter valvular interventions, an expanded grading scale for assessing TR severity was proposed by Hahn & Zamorano (2017); the scale further expands the “severe” grade to include “massive” and “torrential” grades. Echocardiographic evaluation for TR should be performed when the patient is medically optimized in the judgement of a physician with experience in treating right-sided HF. In clinical practice, physicians will consider these quantitative measures, as well as unique patient characteristics, existing comorbidities, and risk factors to determine the most appropriate treatment pathway for patients with TR. Prognosis: Adjusted for other cardiac comorbidities, severe TR more than doubles the risk of mortality compared with no/trivial TR (Offen et al., 2022), with one-year mortality reported in this observational study at 42%. In patients with left ventricular dysfunction, TR was shown to be an independent predictor of increased mortality, with median survival 4.9 years for nonsignificant, 2.3 years for moderate, and 1.6 years for severe TR (Kazum et al., 2019). Treatment and Response to Therapy: Management is determined by the etiology and severity of symptoms, taking into consideration associated conditions such as pulmonary hypertension, presence of Cardiovascular Implantable Electronic Device (CIEDs), comorbidities (e.g., atrial arrhythmias, hyperlipidemia, ischemic heart disease, and diabetes), and left-sided cardiac conditions, including left sided valve disease (Chorin et al., 2020). Treatment of severe or greater TR consists of medical therapy with diuretics and addressing the underlying causes of secondary TR (Hahn et al., 2023; Fender et al., 2018; Messika-Zeitoun et al., 2023); both approaches are Class 2a recommendations in the 2020 American College of Cardiology/ American Heart Association valve guidelines (Otto et al., 2021). Mortality has long been understood to be high in patients undergoing tricuspid valve surgery. Previously reported in-hospital mortality rates were up to 10% to 12% for isolated TV repair/ replacement surgery (Dreyfus et al., 2020; Scotti et al., 2022). However, in patients with isolated TR without comorbidities, as in trauma patients, surgical risk has been reported as low as <1 to 2% (Otto et al., 2021). As such, an argument has been made for earlier surgery in severe TR before significant cardiac remodeling and other systemic sequelae develop (Otto et al., 2021). A recent analysis of the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database evaluated 14,704 isolated tricuspid valve operations performed between 2011 and 2020, showing an increase in volume from 983 cases in 2012 to 2155 cases in 2019 (Chen et al., 2023). Another contemporary analysis of the same database (Thourani et al., 2024) was performed to establish a TV-specific surgical risk model and found 5,553 isolated TV repairs and 8,004 TV replacements performed between 2017 and 2023, with TV replacements primarily performed in younger patients (45.3 ± 18.0 years) and with a higher likelihood of endocarditis. These studies show that surgical mortality has improved in recent years. In the Thourani analysis, operative mortality was 5.6% overall and was similar for repairs and replacements (5.5% and 5.7%, respectively). Mortality with replacement was significantly lower in patients with endocarditis, compared to those with other etiologies of TR (4.1% vs. 7.1%, respectively). The surgical cohort analyzed by Chen et al. excluded patients with endocarditis, tricuspid stenosis, emergent surgery, and previous heart transplants, yielding a group with a median age of 65 years, 40% NYHA Class III/IV HF, and 24% nonelective operations. This cohort had an operative mortality of 7.3% overall, and new permanent pacemaker implant rate of 10.8%. Increased risk for mortality was associated with age > 50 years, chronic lung disease, AF, AS, NYHA Class III/IV HF, nonelective operation, tricuspid valve replacement, annual hospital case volume of 5 or fewer surgeries, and liver dysfunction. Concurrent TV surgery is advised as a Class 1 recommendation for patients undergoing left-sided valve surgery who have severe TR per the 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease Class of Recommendations (Otto et al., 2021). With progressive TR in the setting of tricuspid annular dilation or signs and symptoms of right HF, TV repair concurrent with left-sided valve surgery is given a 2a recommendation, as is isolated TV surgery in patients with right HF and severe primary TR or in those with severe secondary TR due to annular dilation without PH or left-sided disease (Otto et al., 2021). These same guidelines provide a Class 2b recommendation for surgery in asymptomatic patients with severe primary TR in whom RV dilation or systolic dysfunction develop. Similarly, these guidelines include a Class 2b recommendation for isolated TV surgery in patients with symptomatic, severe TR and prior left-sided valve surgery if PH and severe RV systolic dysfunction are absent. Transcatheter Tricuspid Valve Devices: A minimally-invasive, percutaneous, transvenous, catheter-based approach to TV repair has emerged as a potential treatment for TR. The Abbott TriClip System is the first FDA cleared tricuspid transcatheter edge-to-edge repair (T-TEER) device in the U.S. B. Food and Drug Administration Status On April 1, 2024, the FDA approved the TriClip G4 System premarket approval (PMA) application ( P230007 ). This device is indicated for improving quality of life (QoL) and functional status in patients with symptomatic severe TR despite optimal medical therapy (OMT), who are at intermediate or greater risk for surgery and in whom TEER is clinically appropriate and is expected to reduce TR severity to moderate or less, as determined by a multidisciplinary heart team. III. Evidence This section provides a summary of the evidence considered during this review. The evidence presented here includes the pertinent published clinical research on T-TEER for TR. This NCD addresses a family of devices that employ the “edge-to-edge” technique of reducing TR by clamping and apposing the tricuspid leaflets for the purpose of treating TR. This assessment does not address non-TEER devices for addressing TR, nor does it address devices deployed outside of the tricuspid valve. 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 the CMS National Coverage Analysis Evidence Review Guidance Document , published August 7, 2024, or any successor document. A. Evidence Questions The following questions guide our review and analysis of the evidence on the clinical utility of T-TEER for symptomatic TR: Q1: Is the evidence sufficient to conclude that T-TEER is reasonable and necessary for the treatment of Medicare beneficiaries with symptomatic TR? Q2: Is there evidence that specific characteristics or comorbidities make patients more or less likely to benefit from T-TEER? Q3: Are specific treatment conditions necessary to achieve T-TEER outcomes similar to those demonstrated in the clinical studies reviewed in this analysis? B. Technology Assessments CMS did not request an external technology assessment on this topic. C. Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) A MEDCAC meeting was not convened on this topic. D. Clinical Literature Search A systematic literature review focused on T-TEER for TR was undertaken to address the evidence questions defined above. Literature searches were conducted in PubMed and Embase on three occasions, ultimately inclusive of studies through May 18, 2024, with the following search terms: (1) “tricuspid regurgitation” or “tricuspid valve insufficiency,” and (2) “tricuspid edge-to-edge,” (3) “TriClip,” and (4) “tricuspid transcatheter clip.” The review included peer-reviewed English-language medical literature and excluded observational reports with fewer than 30 patients, editorials, and conference abstracts. The focus of the search was on clinical outcomes and safety factors associated with T-TEER. Additional studies were published shortly prior to publication of this final decision memorandum and were added to this analysis. Of the references identified in the searches, 16 publications were deemed eligible for inclusion. Priority was given to the pivotal trials for this analysis. Summary of Evidence Two randomized clinical trials (RCTs), TRILUMINATE Pivotal and the Tri.Fr Randomized Clinical Trial, as reported in five publications and in publicly available reports to the FDA, were reviewed. An overview of the publications with at least one year of follow-up is provided in Table 1 . For a more detailed summary of these and other studies, see Appendix B . Table 1 . Studies Reviewed to Assess Tricuspid Transcatheter Edge-to-Edge Repair (T-TEER) for Tricuspid Regurgitation, arranged by Device and Length of Follow-up Author Year N Study Design Minimum TR Severity a Age (Mean/Median) Female % Follow-Up QoL (Points) Exercise Capacity (6MWT) Functional Status (NYHA class ≤ II) Hospitalization for HF Mortality TriClip von Bardeleben 2023 85 Single arm Moderate 77.8 66% 2y NR +60 meters** BL 33% vs. 2y 81%*** 1y Pre 0.50; 1y Post 0.08 b *** 18.70% Kar 2025 572 RCT Moderate T-TEER 77.1 GDMT 78.2 NR 2y KCCQ-OS Crossover 1y: +7 2y: +10.3 NR NR T-TEER 0.19 Control 0.26*** T-TEER 17.9 Control 17.1 Donal 2025 300 RCT Severe 78 63.7% 1y KCCQ-OS, mean, T-TEER – OMT: +14.5*** T-TEER +31 meters vs. OMT -7 meters NR NR 3.4% Tang 2025 572 RCT Moderate TEER 78.1 GDMT 78.1 TEER 58.9 GDMT 58.9 1y KCCQ-OS, mean, T-TEER – GDMT: +13.5*** T-TEER – GDMT: +31.8 meters *** NR TEER 12.0% GDMT 13.2% TEER 8.6% GDMT 8.0% Arnold 2024 350 RCT Moderate T-TEER 78.0; GDMT 77.6 T-TEER 56.8%; GDMT 52.8% 1y KCCQ-OS, mean: +10.4*** NR NR NR NR Lurz 2024 511 Registry Severe 79 56% 1y KCCQ-OS, mean: +19*** NR BL 21% vs. 1y 75%*** 1y Pre 0.57 vs. 1y Post 0.28 b *** 15.10% Sorajja 2023 350 RCT Moderate TEER 78.0 GDMT 77.8 TEER 56.0% GDMT 53.7% 1y KCCQ-OS, mean, T-TEER – GDMT: +11.7*** T-TEER – GDMT: +17.1 meters NS NR TEER 0.21 b GDMT 0.17 b TEER 9.4% GDMT 10.6% Lurz 2021 85 Single arm Moderate 77.8 66% 1y KCCQ-OS, mean: +20*** +31 meters** BL 31% vs. 1y 83%*** 1y Pre 1.30; 1y Post b 0.78** 7.10% Pascal Wild 2025 1059 Registry Moderate 79 53% 1y MLHFQ, mean: -9 points, [N=188]*** +40 meters*** [N=367] BL 17% vs. 1y 66%*** 16.0% 14.0% Kodali 2023 65 Single arm Moderate 77.4 55.40% 1y KCCQ, mean: BL 53 vs. 30d 71***; 30d 71 vs. 1y 72 NS BL 208 meters vs. 30d 270 meters*** BL 29% vs. 30d 88%***; 30d 88% vs. 1y 92% NS 18.50% 10.80% TriClip and PASCAL Vogelhuber 2024 262 Registry Severe 78.9 51.20% 2y NR NR NR RV normal 29.9%; RV dysfunction 49.1%*** RV normal 27%; RV dysfunction 56.3%*** Stolz 2024 962 Registry Moderate 78.3 50.10% 1y MLHFQ, median: Eligible c +9 vs. Ineligible +7, NS Eligible c +44% vs. Ineligible +43%, NS Eligible c vs. Ineligible, NS Eligible c 14% vs. Ineligible 22%*** Eligible c 15%; Ineligible 25%*** Tanaka 2024 204 Registry Severe 78.9 52.90% 1y NR NR NR 22.60% 10.80% Coisne 2023 308 Registry Severe 76.4 55.8% 1y NR NR NR 15.6% 11% Hanses 2023 102 Single arm Severe 81 51% 1y NR NR NR 13% 25% Russo 2023 298 Registry Moderate 77 ASTR 68%; VSTR 54% 1y NR NR NR NR ASTR 9%; VSTR 28%* Legend : y = years; a The lowest level of TR severity patients included in the publication, as reported by the authors; b events per person-year; c Eligible = patients who met the eligibility criteria for the TRILUMINATE Pivotal randomized controlled trial. Abbreviations : ASTR = atrial secondary tricuspid regurgitation; GDMT = guide-directed medical therapy; HF = heart failure; KCCQ = Kansas City Cardiomyopathy Questionnaire; MLHFQ = Minnesota Living with Heart Failure Questionnaire; PTR = primary tricuspid regurgitation; RCT=randomized controlled trial; RV = right ventricular; SF-36: Short-Form Health Survey; STR = secondary tricuspid regurgitation; T-TEER = tricuspid transcatheter edge-to-edge repair; TR = tricuspid regurgitation; VSTR = ventricular secondary tricuspid regurgitation Only significant results are designated by an asterisk; *p<0.05; **p<0.01; ***p<0.001. E. Assessment of the Evidence i. Trial Design and Enrollment Criteria TRILUMINATE Pivotal The Trial to Evaluate Cardiovascular Outcomes in Patients Treated with the Tricuspid Valve Repair System Pivotal (TRILUMINATE Pivotal) was a prospective, multi-center, open-label RCT evaluating T-TEER using the TriClip Transcatheter Tricuspid Valve Repair system (Sorajja et al., 2023; Arnold et al., 2024). Patients with severe symptomatic TR were enrolled, then assigned to one of two groups (randomized cohort: likely that TR could be reduced to moderate or less; single-arm cohort: likely to reduce TR by ≥ 1 grade but unlikely to reduce to moderate or less). Those in the randomized cohort were randomized 1:1 to receive either T-TEER using the TriClip/TriClip G4 system or medical therapy alone. The randomization goal was up to 550 patients and up to 200 patients were to be included in the single-arm cohort. The primary cohort of TRILUMINATE Pivotal included the first 350 patients randomized, with device patients undergoing procedure within 14 days of randomization. After completion of the 12 month visit, control group participants were eligible to cross over to device provided that they still met inclusion criteria for the intervention. The full randomized cohort of TRILUMINATE Pivotal (n=572) included the primary cohort (n=350) and subsequent enrollment (n=222) with data reported for the 30 day and 12 month visits (Tang et al., 2025). At the 2-year follow-up, findings were reported for all randomized patients in the device and control groups, with analyses stratified for 99 patients remaining in the “pure” control group and 142 patients who crossed over to the device group upon eligibility after 12 months (Kar et al., 2025). Ninety-two percent of patients who crossed over to the device group did so in the first 6 months of the eligibility period. Patients with NYHA functional class II-IV HF secondary to TR were eligible if the local heart team determined that they had been adequately treated per standard of care therapy and stable for at least 30 days, having undergone guideline-directed medical therapy (GDMT), such as diuretics, had undergone device therapy, if appropriate, and were confirmed by a heart team cardiac surgeon to be at intermediate or greater risk for mortality or morbidity with TV surgery. TEE was required for confirmation of TR etiology. Exclusion criteria were numerous and included pulmonary hypertension, severe uncontrolled systemic hypertension, prior TV procedure that may interfere, current indication for left-sided or pulmonic valve correction, CIED leads that may interfere, TV stenosis, left ventricular ejection fraction (LVEF) ≤ 20%, TV not evaluable by echocardiography, or certain TV anatomic features. Other notable exclusions were recent myocardial infarction (MI), percutaneous coronary intervention (PCI), or stroke, hemodynamic instability, chronic dialysis, bleeding disorder/hypercoagulability, peptic ulcer or gastrointestinal (GI) bleeding, infection, or life expectancy of less than 12 months. Trial visits occurred at 30 days, six months, one year, and two years to continue through five years. TRILUMINATE Single Arm TRILUMINATE Single-Arm was a prospective, multi-center, single-arm, interventional study conducted across 21 sites in the US and Europe (Nickenig et al., 2019, Lurz et al., 2021; von Bardeleben et al., 2023) in which 85 trial subjects underwent T-TEER using the TriClip system. Results were reported at six months in Nickenig et al., one year in Lurz et al., and two years in von Bardeleben et al. Subjects had an average age of 77.8 years (SD: 7.9) and the majority were female (66%), had functional TR (84%), and were in NYHA Class III/IV (75%). Tri.Fr Randomized Clinical Trial Tri.Fr was a prospective, multi-center, open-label RCT evaluating T-TEER with the TriClip system combined with OMT to OMT alone (Donal et al., 2025). Patients with severe symptomatic TR who were ineligible for surgical intervention were randomized 1:1 into the intervention group (n=152) or control group (n=148). Inclusion and exclusion criteria were substantively similar to TRILUMINATE although exclusion for LVEF was set at ≤35% rather than ≤20%. Tri.Fr was conducted at 24 centers across France and Belgium. Trial visits occurred at 1, 6, and 12 months. ii. Study Populations TRILUMINATE Pivotal Baseline characteristics of the device and control groups in the primary cohort are shown in Table 2 . All patients had symptomatic TR, and over 95% had a TR severity of severe or greater on the 5-grade scale described by Hahn and Zamorano (2017). Baseline echocardiographic grading of TR was achieved in 173/175 of the randomized T-TEER patients, and 165/175 controls. Most patients were NYHA functional class III or IV. The mean age was approximately 78 years, and both the T-TEER and GDMT groups were mostly female (56% vs. 54%, respectively). As reported in the Summary of Safety and Effectiveness Data (SSED), patients had a wide range of co-morbidities. Most prominent of these in device (D) and controls (C), respectively, were AF (87.4%, 93.1%), hypertension (81.1%, 80.6%), and dyslipidemia (66.9%, 52.6%) (FDA, 2024a). Renal disease was present in 35.4% in both groups. Pulmonary artery systolic pressure ranged from 30-50 mmHg in both groups. At baseline, 37% had undergone mitral or aortic valve intervention, including 15.4% aortic valve intervention, 11.4% transcatheter mitral valve repair, 6.6% surgical mitral valve repair, 5.4% mitral valve replacement, and one prior TV repair (T-TEER group). Table 2 . Comparison of baseline patient characteristics in the TRILUMINATE Pivotal primary cohort TRILUMINATE Pivotal TriClip (N=175) Control (N=175) Age (year) – mean (SD) 78.0 (7.4) 77.8 (7.2) Female (%) 56 53.7 NYHA Class II, n (%) 71 (40.6) 78 (44.6) NYHA Class III, n (%) 100 (57.1) 91 (52.0) NYHA Class IV, n (%) 4 (2.3) 6 (3.4) Severity of TR, n (%) N=173 N=165 Moderate 4 (2.3) 2 (1.2) Severe 44 (25.4) 49 (29.7) Massive 37 (21.4) 30 (18.2) Torrential 88 (50.9) 84 (50.9) Legend : NYHA = New York Heart Association; TR = Tricuspid regurgitation For reference, the baseline characteristics for the full cohort are reported in Table 3 . Baseline characteristics were similar between the initial cohort of patients included in Sorajja et al., 2023 and the full cohort included in Tang et al., 2025. Baseline characteristics for patients in the crossover and “pure” control groups at the 2-year follow-up are also included in Table 3 (Kar et al., 2025). Severity of TR at 2 years is reported for those patients who did not cross over to the device or undergo tricuspid valve surgery (Kar et al., 2025). Although baseline characteristics for the different treatment conditions were similar overall for patients enrolled in TRILUMINATE Pivotal, the patients who crossed over to the device group differed from the “pure” control patients at the first-year follow-up. Patients in the crossover group were more likely to experience torrential TR than “pure” controls (65.2% vs. 41.5%, respectively), more likely to be in NYHA class III/IV (47.5% vs. 30.4%), and more likely to have experienced decreases in QoL and increases in HF hospitalizations (Kar et al., 2025). Table 3 . Comparison of baseline patient characteristics in the TRILUMINATE Pivotal full randomized cohort and crossover vs. “pure” control groups TRILUMINATE Pivotal Tang et al., 2025 Kar et al., 2025 TriClip (N=285) Control (N=287) Crossover (N=142) “Pure” Control (N=99) Age (year) – mean (SD) 78.1 (7.9) 78.1 (7.6) 77.1 (8.3) 78.2 (6.8) Female (%) 58.9 58.9 NR NR NYHA Class II, n (%) Reported as Class III/IV NYHA Class III, n (%) 160 (56.1) 155 (54.0) 77 (54.2) 46 (46.5) NYHA Class IV, n (%) Severity of TR, n (%) N=279 N=274 N=111 N=44 Moderate 6 (2.2) 4 (1.5) 2% 0% Severe 70 (25.1) 78 (28.5) 30% 43% Massive 67 (24.0) 51 (18.6) 18% 14% Torrential 136 (48.7) 141 (51.5) 51% 43% Legend : NR = Not reported; NYHA = New York Heart Association; TR = Tricuspid regurgitation TRILUMINATE Single Arm Baseline characteristics of patients are shown in Table 4 . TR severity was severe or greater in 94% of patients. The mean age was approximately 78 years, and the majority of patients were female (66%). Comorbidities included AF (92%), hypertension (86%), and renal disease (46%). Mean pulmonary artery systolic pressure was 38.9 (SD 16.0) mmHg. At baseline, 11% had undergone previous aortic intervention and 33% had undergone previous mitral intervention, including 32.1% percutaneous repair, 28.6% surgical repair, 25% surgical replacement, and 7.1% percutaneous replacement. Table 4 . Baseline patient characteristics in TRILUMINATE Single Arm TriClip (N=85) Age (year) – mean (SD) 77.8 (7.9) Female (%) 56 (66) NYHA Class III/IV (%) 64 (75%) Severity of TR, n (%) N=84 None or trace 0 Mild 0 Moderate 5 (5.9) Severe 24 (29.4) Massive 24 (28.2) Torrential 31 (36.5) Legend : NYHA = New York Heart Association; TR = Tricuspid regurgitation Tri.Fr Randomized Clinical Trial Baseline characteristics of the device and control groups are shown in Table 5 . All patients had symptomatic TR, and 91% had a TR severity of massive or greater on the 5-grade scale described by Hahn and Zamorano (2017). Most patients were NYHA functional class II. The mean age was approximately 78 years, and both the T-TEER+OMT and OMT groups were mostly female (65.5% vs. 62.8%, respectively). Patients had a wide range of co-morbidities. Most prominent of these in intervention and controls, respectively, were AF (94.1%, 95.9%), atrial arrhythmia (74.3, 81.1), and hypertension (69.7%, 68.9%). Mean pulmonary artery systolic pressure was approximately 22.4 mmHg in both groups. At baseline, 18.4% in the intervention group and 12.2% in the control group had undergone prior PCI. About 10% had undergone any prior aortic intervention, 5% underwent surgical mitral valve repair, and 8.6% underwent percutaneous mitral valve repair (Donal et al., 2025). Table 5 . Comparison of baseline patient characteristics in Tri.Fr Tri.FR T-TEER+OMT (N=152) OMT alone (N=148) Age (year) – mean (SD) 78.3 (6.4) 78.7 (6.4) Female (%) 65.5 62.8 NYHA Class II, n (%) 93 (61.2) 77 (52.0) NYHA Class III, n (%) 58 (38.2) 64 (43.2) NYHA Class IV, n (%) 1 (0.66) 4 (2.70) Legend : NYHA = New York Heart Association iii. Background Therapy TRILUMINATE Pivotal As shown in Table 6 , the vast majority of patients in TRILUMINATE Pivotal received diuretics, a majority received β-receptor antagonists, 37-39% received ACE-I, ARB, or ARNI, and fewer than 10% received vasodilators (Sorajja et al., 2023). Patients were required to receive stable GDMT for HF for 30 days or more prior to the beginning of the study. The full cohort of patients described by Tang and colleagues (2025) was similar to the initial cohort. Similar to their increase in HF symptoms, patients who crossed over to the device group showed an increase in mean diuretic dose from baseline (64.2 mg ± 51.7) to one year (88.4 mg ± 181.0). At year two, diuretic dosage was lower than year one in this group, but did not return to baseline levels (85.6 mg ± 92.3) (Kar et al., 2025). Table 6 . Baseline rates of guideline-directed medical therapy in the TRILUMINATE Pivotal RCT. TRILUMINATE Pivotal Sorajja et al., 2023 Tang et al., 2025 TriClip (n=175), % Control (n=175), % TriClip (n=285), % Control (n=287), % β-receptor antagonist 65.1 65.7 69.5 72.5 ACE-I, ARB, or ARNI 38.9 37.7 ACE-I 13.7 12.5 ARB 27.0 32.8 Vasodilator 8.0 9.7 8.1 10.8 Diuretic 86.9 92.0 96.1 98.3 Legend : ACE-I: angiotensin-converting enzyme inhibitors; ARB: angiotensin II receptor blocker; ARNI: Angiotensin Receptor-Neprilysin Inhibitor. Tri.Fr Randomized Clinical Trial All patients enrolled in Tri.Fr received OMT throughout the trial. Most patients received diuretics, and about 72% received β-receptor antagonists. Table 7 shows baseline medication use. Patients were required to be stable on OMT for at least 30 days prior to trial. Table 7 . Baseline rates of OMT in Tri.Fr Tri.FR T-TEER+OMT (N=152), % T-TEER+OMT (N=152), % β-receptor antagonist 70.4 74.3 ACE-I, ARB, or ARNI 46.0 54.0 Vasodilators 8.0 9.7 Loop Diuretics 95.4 96.6 Thiazide 9.21 11.5 Legend : ACE-I: angiotensin-converting enzyme inhibitors; ARB: angiotensin II receptor blocker; ARNI: Angiotensin Receptor-Neprilysin Inhibitor. iv. Intervention Setting TRILUMINATE Pivotal The TRILUMINATE Pivotal trial was conducted across 68 sites, randomizing 572 subjects in the US, Canada, and Europe. Patients were adjudicated as eligible by a local heart team that consisted of specialists board-certified in cardiac surgery, interventional cardiology, echocardiology, and HF. Severity of TR was confirmed by an independent echocardiography laboratory to confirm eligibility. All sites were required to have experience in transcatheter edge-to-edge repair of the mitral valve (M-TEER) of at least 50 procedures (FDA, 2024b). Up to three roll-in patients were allowed per implanter with no prior TriClip experience prior to randomization (FDA, 2024a). Outcomes in the roll-in cohort (n=141) were presented to the FDA. Nearly 30% of all subjects were enrolled at the top five high-volume sites. Tri.Fr Randomized Clinical Trial Tri.Fr was conducted across 24 tertiary centers, randomizing 300 subjects in France and Belgium. Patients were adjudicated as eligible by a centralized CORELAB and a local clinical eligibility committee of at least five members including a cardiovascular surgeon, an interventional cardiologist, two HF specialists, and an imager to perform echocardiograms to be sent to the CORELAB. Severity of TR was confirmed by the CORELAB, which was blind to patient group allocation. All sites had performed at least 10 T-TEER procedures before trial enrollment began. v. Endpoints TRILUMINATE Pivotal The primary endpoint was a composite of all-cause mortality or TV surgery, HF hospitalization, and QoL assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at one year, analyzed on an intent to treat (ITT) basis as a Finkelstein-Schoenfeld win ratio using unmatched pairs. Secondary endpoints, evaluated in a hierarchical order if results for the primary endpoint were significant, included freedom from major adverse events (MAE) at 30 days post procedure in the attempted-procedure group, change in KCCQ at one year (ITT), TR reduction to moderate or less at 30 days (ITT), and change in 6-minute walk distance (6MWD) at one year (ITT) (Sorajja et al., 2023; Tang et al., 2025). Procedural endpoints analyzed were Technical Success (exit from procedure room alive with successful access, delivery, and retrieval of the device delivery system, completed deployment and correct positioning of a clip, and no need for additional unplanned surgery or intervention related to the procedure); Device Success (alive with original intended clips in place, no additional surgery or intervention related to the index procedure, at least one grade improvement in TR severity, no embolization or single leaflet attachment, and absence of device-related complications at 30 days post-procedure); and Procedural Success (device success with no device- or procedure-related SAEs at 30 days post-procedure) (Sorajja et al., 2023). Two-year secondary endpoints were recurrent HF hospitalizations (ITT), and freedom from all-cause mortality, TV surgery or intervention (ITT). MAE was inclusive of cardiovascular death, new-onset kidney failure, endocarditis treated with surgery, and nonelective CV surgery for device-related adverse event. Endpoints were analyzed in a prespecified order if the endpoint for recurrent HF hospitalizations was met: Freedom from all-cause mortality followed by TV surgery or intervention. Analyses that assessed potential changes in TR severity and QoL did not include patients who underwent TV surgery (Kar et al., 2025). In the second publication on TRILUMINATE Pivotal, the primary endpoint was the one-year change in QoL, as measured by the score on the KCCQ (Arnold et al., 2024). TRILUMINATE Single Arm The primary efficacy endpoint in TRILUMINATE Single-Arm was a TR reduction of ≥1 grade at 30 days, which was achieved by 86% of 83 patients and exceeded the performance goal of 35% (Nickenig et al., 2019). The percentage of patients who met the endpoint was sustained from 30 days to the two-year follow-up (86% vs. 85%, respectively; Nickenig et al., 2019; von Bardeleben et al., 2023) and the percentage of patients with a TR severity ≤ moderate increased from baseline to two years (4% vs. 60%, respectively, p<0.0001), and the improvement remained unchanged from 30 days to the two-year follow-up (63% vs. 60%, p=0.90; von Bardeleben et al., 2023). Of the 39 patients with the greatest TR severity (torrential or massive) at baseline, 90% experienced a TR reduction of ≥1 grade after one year (Nickenig et al., 2019, Lurz et al., 2021; von Bardeleben et al., 2023). The primary safety endpoint in TRILUMINATE Single-Arm was the proportion of patients with MAEs at six months, which was 4% of 84 patients and significantly below the 39% performance goal (p<0.0001; Nickenig et al., 2019). The percentage of patients who experienced MAEs was driven by CV mortality (n=2) and new onset renal failure (n=1). At one year, the rates for MAEs remained relatively low, with 7% of 84 patients experiencing CV mortality (n=4), stroke (n=1), or new onset renal failure (n=1) (Lurz et al., 2021). Single-leaflet device attachment was reported in 7% without clinical findings or worsening of TR. At two years, 18% of patients experienced MAEs, which was over twice the rate at one year (von Bardeleben et al., 2023). All-cause mortality was relatively low at six months (5% of 84) and one year (7% of 84), but more than doubled at two years (17%). Other than all-cause mortality, the most common AE at six months, one year, and two years was major bleeding (six months: 11% of 84, one year: 12% of 84, two years: 12%). Hospitalization for HF was significantly lower for one-year post-TEER vs. one-year pre-TEER (0.78 events/P-Y vs. 1.30 events/P-Y, p=0.003) and two years post-TEER vs. one-year pre-TEER (0.66 events/P-Y vs. 1.30 events/P-Y, p<0.0001). An analysis of mortality/HF hospitalization at one year stratified by TR severity among 70 patients revealed that patients with a reduction to ≤ moderate severity at 30 days post-TEER had a 60% lower rate of mortality/HF hospitalization compared to those with ≥ severity at 30 days (HR: 0.40, p=0.034). This finding suggests a correlation between mortality