National Coverage Analysis (NCA) Proposed Decision Memo

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

CAG-00468N

Expand All | Collapse All

Decision Summary

DATE:     July 2, 2025

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 Opens in a new window, published August 7, 2024 (the “CED Guidance Document”). 

  1. Sponsor/Investigator:  The study is conducted by sponsors/investigators with the resources and skills to complete it successfully.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Sensitivity Analyses:  Sponsors/investigators will demonstrate robustness of results by conducting pre-specified sensitivity testing using alternative variable or model specifications as appropriate.
  14. 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).
  15. 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.
  16. 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.
  17. 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.

Proposed Decision Memo

DATE:     July 2, 2025

Table of Contents

  1. Decision
    1. Decision
    2. Coverage Criteria
      1. Patient Criteria
      2. Physician Criteria
      3. CED Study Criteria
    3. Other Uses of T-TEER
  2. Clinical Review
    1. Background
    2. Food and Drug Administration Status
  3. Evidence
    1. Evidence Questions
    2. Technology Assessments
    3. Medicare Evidence Development and Coverage Advisory Committee (MEDCAC)
    4. Clinical Literature Search
    5. Assessment of the Evidence
      1. Trial Design and Enrollment Criteria
      2. Study Populations
      3. Background Therapy
      4. Intervention Setting
      5. Endpoints
      6. RCT Study Quality and Risk of Bias
      7. Synthesizing the Clinical Trial Evidence
      8. Evidence from observational studies and relevance to Medicare beneficiaries
      9. Limitations of Evidence
      10. Considerations for Further Research
    6. Evidence-Based Guidelines
    7. Professional Society Recommendations / Consensus Statements / Other Expert Opinion
    8. Appropriate Use Criteria
    9. Public Comment
      1. Support for Medicare Coverage for T-TEER
      2. Non-Coverage for T-TEER
      3. Coverage Indications
      4. Physician Criteria
      5. Institutional Criteria
      6. Volume Criteria
      7. CED Criteria for T-TEER
      8. Miscellaneous Comments
  4. CMS Coverage Analysis
    1. CMS Coverage Authority
    2. CMS Analysis for Coverage of T-TEER for TR
      1. Rationale for Coverage Requirements for T-TEER for TR (Patient, Physician, and CED Study Criteria)
      2. Evidence Questions – Answered
    3. Benefit Category
    4. Shared Decision-Making
  5. History of Medicare Coverage
    1. Current National Coverage Request
    2. Timeline of NCA Milestones
  6. Appendices

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 Opens in a new window, published August 7, 2024 (the “CED Guidance Document”). 

  1. Sponsor/Investigator:  The study is conducted by sponsors/investigators with the resources and skills to complete it successfully.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Sensitivity Analyses:  Sponsors/investigators will demonstrate robustness of results by conducting pre-specified sensitivity testing using alternative variable or model specifications as appropriate.
  14. 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).
  15. 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.
  16. 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.
  17. 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/m2), 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 Opens in a new window).  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 Opens in a new window, 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 Severitya 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 0.08b***

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 0.28b***

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 0.21b
GDMT 0.17b

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 Postb 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: Eligiblec +9 vs. Ineligible +7, NS

Eligiblec +44% vs. Ineligible +43%, NS

Eligiblec vs. Ineligible, NS

Eligiblec 14% vs. Ineligible 22%***

Eligiblec 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; aThe lowest level of TR severity patients included in the publication, as reported by the authors;bevents per person-year; cEligible = 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/HF hospitalization and reduction of TR severity after two years.

Tri.Fr Randomized Clinical Trial

The primary endpoint was a composite of change in NYHA class, patient-reported change in patient global assessment (PGA), or occurrence of major cardiovascular events at 12 months.  NYHA class was assessed by an independent observer at follow-up visits.  The measure for major cardiovascular events was defined as death or HF hospitalization (unplanned).  The composite was categorical, rated as improved, unchanged, or worsened and analyzed using ITT.  Secondary endpoints were TR grade, change in KCCQ score, PGA, major cardiovascular events, cardiovascular mortality, and a hierarchical composite that included all-cause mortality or tricuspid valve surgery, time to HF hospitalization, and improvement of KCCQ score of at least 15 points.  Analysis of secondary outcomes followed predefined hierarchical testing such that each secondary outcome would be tested only if the previous outcome reached significance.

vi.              RCT Study Quality and Risk of Bias

A formal quality assessment using the US Preventive Services Task Force’s (USPSTF) Criteria for Assessing Internal Validity of Individual Studies tool was performed for the TRILUMINATE Pivotal study, which received a rating of “Good”.  Factors contributing to this rating included adequate randomization, comparable treatment groups at baseline, an acceptable overall completion rate (86%), and a <10% difference in attrition between treatment groups.  Intention-to-treat analysis was used for all endpoints except freedom from MAEs.  While patient blinding was not inherently possible due to the nature of treatment, efforts were made to mitigate the risk of performance and detection biases by independent adjudication of AEs and blinded QoL assessors.  However, echocardiogram assessors were not blinded to treatment assignment and thus, could serve as a potential source of bias.  Notably, patients were assessed for final study eligibility by a Heart Team and were excluded if deemed unlikely to show sufficient reduction in TR severity.  Moreover, patients underwent mandated right heart catheterization to confirm appropriate medical management and TR as the likely source of their symptoms.  Aside from the rigorous selection of patients, another limitation acknowledged by the authors was the enrollment of patients with fewer overall comorbidities compared to prior studies.  This might have contributed to the favorable early survivorship observed.  Although the follow-up reports at one and two years were not formally assessed, it is important to consider the impact of patients crossing over to the device condition after the year one visit on subsequent findings.  The most important factors to consider at later time points will be the small number of patients remaining in the control group as randomized (n=99), and that the patients who crossed over to the device condition were sicker than the patients remaining in the control group.  As a result, the control group may not be comparable to the T-TEER group.

Tri.Fr Randomized Clinical Trial

A formal quality assessment was not performed.  Tri.Fr was an open-label study, which is subject to similar biases as outlined above for TRILUMINATE.  Randomization and allocation concealment appeared adequate, and the two groups were comparable at baseline. ITT analysis was used.  The severity of TR and suitability for T-TEER were adjudicated by a centralized echocardiography lab, and staff were blind to treatment allocation.  The authors noted that the lack of blinding by patients and other clinical staff may contribute to bias when interpreting patient reported outcome measures.  The authors also noted as a limitation that Tri.Fr was investigator initiated and supported by a limited grant from the French Ministry for Health.

Other studies

A formal quality assessment was not performed on the remaining studies due to either their observational and/or single-arm study design.  These study types tend to have low internal/external validity with inherent biases and thus, would likely render the overall evidence as poor quality.  Additionally, single-center studies may have introduced various forms of bias (e.g., patient selection), enrolled potentially homogenous populations that affect their applicability to the US population, and may not be representative of providers’ varying levels of skill in performing T-TEER.  Studies with smaller sample sizes may not have been adequately powered, and follow-up periods were relatively short for the majority of studies.

vii.           Synthesizing the Clinical Trial Evidence

TRILUMINATE Pivotal Results

Trial results are reported in Table 1 and baseline characteristics of the study groups are provided in Tables 2 and 3.

Of the 175 subjects in the primary cohort who were randomized to the device arm, three patients withdrew before the procedure was attempted.  Device implantation was attempted in 172 patients and was successful in 170 patients (97.1%).  A single clip was deployed in 10.5%, two clips were deployed in 61.0%, three were deployed in 24.4%, and four were deployed in 2.9% of device patients.

At one-year follow-up, the primary endpoint win ratio favored the T-TEER group (WR 1.48, 95% CI: 1.06 to 2.13, p=0.02), primarily driven by performance on the KCCQ-Overall Summary score.  Approximately 50% vs. 26% of patients in the T-TEER and GDMT groups, respectively, reported overall QoL improvement on the KCCQ measure at one year (p<0.0001).  The remaining components of the primary endpoint—all-cause mortality or TV surgery (9.4% vs. 10.6%, p=0.75) and HF hospitalization (0.21 vs. 0.17 events/P-Y, p=0.41) for the T-TEER and GDMT groups, respectively—did not significantly differ between groups at one year.  Sensitivity analyses conducted for the as-treated (WR: 1.59, 95% CI: 1.13 to 2.31), per-protocol (win ratio: 1.44, 95% CI: 1.00 to 2.11), and post-COVID diagnosis (win ratio: 1.43, 95% CI: 1.02 to 2.04) groups were relatively consistent with the intention-to-treat findings.

Technical success was 98.8%, with 88.9% 30-day device success reported in the 162 patients for whom all relevant data were available.  Single-leaflet device attachment occurred in 11 patients, three had no reduction in TR, and three required surgery or intervention within 30 days.  One death occurred within 30 days in the device group.  Procedural success was further diminished by the three subjects with device- or procedure-related SAEs, including single leaflet attachment, ruptured chordae, and an access site complication.

In the device vs. control groups, respectively, through 12 months, adverse events included all-cause mortality (8.6 vs. 7.4%), CV mortality (6.3 vs 4.6%), hospitalizations (36.0 vs. 34.3%), non-CV hospitalization (21.7 vs. 21.1%), and major bleeding (5.7 vs. 1.7%).  There was one TV surgery due to an unsuccessful T-TEER procedure.  At the 30-day follow-up, 169 patients in the attempted-procedure population (98.3%) were free from MAEs, compared with a 90% performance goal (Sorajja et al., 2023).

As reported in Sorajja et al., 2023, 161 device patients and 146 control patients had echocardiography available at 30 days, and TR was reported as moderate or less in 87.0% of device and 4.8% of control patients studied.  This difference persisted at one-year post-procedure (88% vs. 6%, respectively).

Diuretic dosages did not decline at one year in the device group, and IV diuretic usage was higher in the device group at one year, confounding understanding of the impact of the intervention relative to medication management.

Analysis of the KCCQ-Overall Summary scores showed an improvement in QoL for the T-TEER group exceeding that of the medical therapy group by an average of 11.7 points (95% CI: 6.8 to 16.6, p<0.001).  Change in 6MWD was -8.1±10.5 m in the device group, compared with -25.2±10.3 in the control group, a non-significant difference (p=0.25).  In a post-hoc analysis, improvements in QoL were correlated with residual TR severity, with greater increases in KCCQ score with reduced TR severity.  However, as shown in the SSED analysis, large standard deviations were observed in each category assessed (FDA, 2024a).

In the most recent analysis of TRILUMINATE Pivotal focused on QoL, the KCCQ-Overall Summary score improvement reported in the T-TEER group exceeded that in the control group by 10.4 points (95% CI: 6.3-14.6, p<0.001) at the one-year follow-up (Arnold et al., 2024).  The analysis highlighted device vs. control group outcomes for all KCCQ domain scores except for mental health (physical limitations, 7.3 points, p=0.003; total symptoms, 6.8 points, p=0.004; QoL, 14.1 points, p<0.001; social limitation, 14.0 points, p<0.001; and the physical component summary, 5.2, p<0.001).

At one year follow-up of the full cohort (Tang et al., 2025), the findings were similar to the one-year findings reported in Sorajja et al. (2023).  The primary composite endpoint showed treatment efficacy with the T-TEER device relative to GDMT alone (win ratio 1.8; 95% CI: 1.4 to 2.5), which was driven by improvements in QoL.  All-cause mortality or TV surgery (90.6% vs. 89.9%), or freedom from HF hospitalizations (88.0% vs. 86.8%) did not differ between T-TEER and GDMT, respectively.  TR severity was significantly improved in the T-TEER group, with 88% of patients categorized as Moderate or less relative to 8% of GDMT patients.  Similarly, NYHA functional class was improved in the T-TEER group, with a greater percentage of patients moving to Class I/II than controls (85.5% vs. 60.1%; p<0.0001).

When comparing the primary cohort (n=350) with the subsequent enrollment cohort (n=222), the components for the composite outcome did not differ between the two populations with the exception of HF hospitalizations.  There were lower rates of HF hospitalizations in the device group subsequent to the primary analysis (annualized rate 0.09 in the subsequent enrollment cohort vs. 0.22 in the primary cohort; p=0.04).  Further, in the subsequent enrollment cohort, HF hospitalizations were lower in the T-TEER group relative to the GDMT group (annualized rate 0.09 vs. 0.20; p=0.04).  The authors suggest that relatively low rates overall for HF hospitalization may have impacted the findings, along with potential spurious statistical findings resulting from multiple comparisons (Tang et al., 2025).

At two years, Kar et al. (2025) report on the prespecified endpoints of recurrent HF hospitalizations and a composite endpoint consisting of freedom from all-cause mortality and TV surgery/intervention.  In the ITT analysis, HF hospitalizations were lower in the T-TEER group relative to controls (HR: 0.72; 95% CI: 0.53 to 0.98), indicating a relative risk reduction of 28% for the T-TEER group.  For the composite endpoint, greater benefit was seen in the T-TEER group relative to controls in the ITT analysis, with 22.4% experiencing any component of all-cause mortality, TV surgery, or TV intervention relative to 70.7% of controls.  This effect was driven by a higher rate of TV interventions in the control group (61.5%) who crossed over to receive the device.  Freedom from all-cause mortality and TV surgery did not differ between the two groups.  Improvements in TR severity and QoL in the T-TEER group were sustained at the two-year follow-up (Kar et al., 2025).

At one (Tang et al., 2025) and two years (Kar et al., 2025) of follow-up in the ITT population, mortality, hospitalizations, and adverse events were similar between T-TEER and controls, with the exception of TV interventions in the control group between year one and year two.  As noted above, a majority of these patients crossed over to the T-TEER group.

In summary, the results of TRILUMINATE Pivotal reported up to two years post-procedure suggest that TriClip implantation improves TR severity, QoL, and recurrent HF hospitalization rate (at two years), but not all-cause mortality/TV surgery or HF hospitalization for patients with severe TR who are receiving GDMT and are at intermediate or greater risk for surgery.  TR severity and QoL were significantly improved in the T-TEER group vs. the GDMT group at 30 days and the improvements were sustained two-years post-procedure.  For QoL, the difference between the two groups exceeded 10 points, which is greater than the estimated minimal clinically important difference (MCID) in the KCCQ of five points or less (Butler et al., 2020).  Improvement in functional capacity was greater for the T-TEER group than the GDMT group in the full cohort at one year (Tang et al., 2025).  However, all-cause mortality/TV surgery and HF hospitalization were comparable for the two groups throughout the study period.  Although a large percentage of patients in the control group elected to cross over to the device condition, the pattern of findings remained the same.  The authors caution that the small number of patients remaining in the “pure” control group will limit the interpretation of data analyses at later time points, particularly as patients remaining in the “pure” control group had less severe illness than patients who crossed over.

TRILUMINATE Single-Arm Results

Trial results are reported in Table 1 and baseline characteristics of the study group are provided in Table 4.

Evaluable TR severity was available for 48 of the 85 subjects at two years.  Attrition was due to 14 deaths, six withdrawals, three missed visits, and unreadable echocardiographic imaging in 14 subjects.  Reduction to ≤ moderate TR was achieved in 29 at two years, with TR reduction of at least one grade in 41.  Thirty-day TR reduction was sustained in 36 of evaluable subjects, 12 of whom demonstrated further reduction in TR at two years.  Increase in TR at two years was observed in 12 subjects, with six exceeding moderate.  The percentage of patients in NYHA Class I/II increased from 33% to 85% from baseline to 30 days and was 81% at two years (von Bardeleben et al., 2023).  The average distance for the 6MWT increased by 60 meters (p<0.01), and the average KCCQ-HF score increased by 13 points (p<0.0001) from baseline to two years (von Bardeleben et al., 2023).

Some echocardiographic parameters, such as right ventricular end diastolic diameter (RVEDD), tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC), suggested favorable remodeling of the right heart following T-TEER, with changes occurring predominantly during the first 30 days post-procedure.  However, tricuspid annular diameter septal-lateral, right atrial volume, RV fractional area change (RVFAC), RV systolic pressure, RV global longitudinal strain, and LVEF did not significantly change between baseline and two years.

Tri.Fr Randomized Clinical Trial Results

Of 152 subjects randomized to the device arm, three patients withdrew consent and one patient died before the procedure was attempted.  Device implantation was attempted in 148 patients and was successful in 144 patients (97.3%).  Two or more clips were deployed in 83.1% of device patients.  One patient died 13 days post-procedure as a result of cardiac arrest and subsequent coma.

At one-year follow-up, improvements in the primary endpoint composite score were greater (p<0.001) in the T-TEER+OMT group (74.1%) relative to the OMT alone group (40.6%; probability of better rank: 0.67; 95% CI: 0.68 to 0.78).  These changes in the composite score were related primarily to improvement in NYHA class and patient-reported PGA scores.  The two groups did not differ with respect to rates of cardiovascular-related hospitalizations or deaths.

Hierarchical analysis of secondary endpoints found that TR severity of massive or torrential was lower in the T-TEER+OMT group relative to the OMT alone group (6.8% vs. 53.5%; p<0.001).  The mean KCCQ score was higher in the T-TEER+OMT group than in the OMT alone group (absolute difference: 14.5±27.2 points; p<0.001).  Similarly, more patients reported improvements in health, as measured using the PGA, in the T-TEER+OMT group relative to the OMT alone group (probability of better rank: 0.68; 95% CI: 0.63 to 0.74; p<0.001).

The findings of Tri.Fr are similar to those of the TRILUMINATE trial for improvements in both QoL scores and TR severity but not in cardiovascular mortality or HF hospitalizations.  Patients enrolled in Tri.Fr were highly selected, with similar inclusion/exclusion criteria to those enrolled in TRILUMINATE.  Patients enrolled in Tri.Fr, however, had less severe HF symptoms than other studies.  Planned follow-up for Tri.Fr will be reported at two- and five-years post-procedure.

viii.        Evidence from observational studies and relevance to Medicare beneficiaries

Uncontrolled observational studies, including registry-based studies, were identified in this analysis.  An overview of the studies with at least one year of follow-up is provided in Table 1.  Detailed study characteristics and outcomes are provided in Appendix B.

Publications reporting solely on TriClip

bRIGHT PAS

bRIGHT PAS, a large registry study, was examined in a total of three publications.  The study began in 2020 and was designed as a real-world, post-market registry to satisfy European CE Mark requirements for the safety and effectiveness of TriClip.  Two publications that utilized data from the bRIGHT registry evaluated the short-term outcomes of TriClip implantation at 30 days post-procedure, and the latest publication examined outcomes at the one-year follow-up.

Lurz et al. (2024) examined the one-year outcomes for the 511 patients from the bRIGHT registry.  The percentage of patients with a TR grade of moderate or less did not change significantly from 30 days to one year (85% vs. 81%, respectively, p=0.69).  HF hospitalization rate for the one-year pre- vs. post-device was significantly reduced (events/person-years: 0.57 vs. 0.28, respectively, p<0.0001).  There was no device embolization at one year, but the number of single leaflet device attachments increased from 3.5% at 30 days to 3.9% at one year, as did the number of reinterventions (30 days, 0.2% vs. one year, 3.3%), all-cause mortality (30 days, 1.0% vs. one year, 15.1%) and cardiovascular mortality (30 days, 0.8% vs. one year, 8.8%).  Significant predictors of survival at one year using Kaplan-Meier estimation included aspartate transaminase (OR [95% CI]: 1.26 [1.00, 1.58], p=0.047), female sex (OR [95% CI]: 0.55 [0.33, 0.91], p=0.02), moderate or less residual TR (OR [95% CI]: 0.32 [0.19, 0.55], p=0.02), serum creatinine (OR [95% CI]: 1.85[1.42, 2.39], p<0.001), LVEF (OR [95% CI]: 0.71 [0.56, 0.91], p=0.007), and baseline KCCQ Overall Summary, OR [95% CI]: 0.73 [0.55, 0.96], p=0.007).  Site experience with performing T-TEER, RV TAPSE, alanine transaminase, and Systolic Pulmonary Artery Pressure (sPAP) were not significant predictors of survival at one year (all p > 0.05).

Publications reporting on the combined use of TriClip and PASCAL (Edward Lifesciences; Irvine, CA)

Hanses et al. conducted a single-arm study in Germany with 102 patients implanted with TriClip or PASCAL.  A subgroup analysis was performed for patients with a low vs. high right ventricular cardiac power index (RVCPi).  At 30 days, there were no differences between the low and high groups for all-cause mortality (12% vs. 7%, p=0.5), the rehospitalization of patients with congestive HF (9% vs. 1%, p=0.09), or any of the safety events.  However, one-year all-cause mortality was lower in the low RVCPi group than the high RVCPi group (18% vs. 38%, log-rank p=0.024) (Hanses et al., 2023).

TriValve Registry

The TriValve registry was a large, international registry with patients at 24 centers in Europe and North America.  Two included publications examined outcomes from the TriValve registry at the one-year follow-up.

Coisne et al. conducted a study of the TriValve registry with a total of 308 patients who were implanted with MitraClip, TriClip, or PASCAL.  The study sought to determine if the clinical outcomes were associated with the TV gradient at discharge.  The highest quartile of the TV gradient had the highest residual TR ≥ 3 at discharge (Q1=10.5%, Q2=10.5%, Q3=23.1%, and Q4=28.0%; p<0.01) and the lowest procedural success rate (defined as the patient was alive, the device successfully implanted, and residual TR ≤ 2) (Q1=89.5%, Q2=86.8%, Q3=76.9%, and Q4=72%, p=0.02).  However, the TV gradient was not related to the primary or secondary endpoints.  The primary composite endpoint of all-cause mortality or HF hospitalization occurred in 20.4% of patients, and the secondary endpoints of all-cause mortality and HF hospitalization occurred in 11.0% and 15.6%, respectively, of patients.  In addition, no differences were revealed by TV gradient for the NYHA functional class before T-TEER (p=0.78), at 30 days (p=0.84), or at the last follow-up (p=0.63) (Coisne et al., 2023).

Russo et al. conducted a TriValve registry study to compare the clinical characteristics and outcomes of patients with atrial secondary TR (ASTR) and ventricular secondary TR (VSTR).  A total of 298 patients (n: ASTR 65, VSTR 233) implanted with MitraClip, TriClip, or PASCAL were followed through 12 months.  There were no differences between the ASTR and VSTR groups for procedural success, which was the primary endpoint (80% vs. 83%, respectively; p=0.56).  However, the survival rate, which was defined as the time from the date of T-TEER until death due to any cause, was higher for the ASTR group than the VSTR group (91% vs. 72%, log-rank p=0.02).  However, in a multivariate analysis to predict mortality risk, the only significant predictor was acute procedural risk (HR [95% CI]: 0.41 [0.17–0.96], p=0.04); VSTR vs. ASTR, age of 75 or above, elevated NT-proBNP, TAPSE < 17 mm, and high-dose diuretics were all insignificant (all p > 0.05).  For safety outcomes, there were also no differences between the two groups (Russo et al., 2023).

Bonn Registry

The Bonn registry was a large, international registry at the Heart Centre in Bonn.  Two included publications examined outcomes from the Bonn registry at the one-year follow-up.

Tanaka et al. conducted a study of the Bonn registry that included 204 patients implanted with MitraClip, TriClip, or PASCAL.  The study examined post-procedural changes in RV function and its association with clinical outcomes.  Overall, procedural success occurred in 78% of patients, with success defined as successful implantation combined with a reduction in TR severity to two or less upon discharge.  For the study’s primary composite outcome, which was mortality or hospitalization due to HF at the one-year follow-up, the endpoint was more likely to occur for patients with RV dysfunction at baseline (defined as RVFAC < 35%) than those with normal RV function (46.8% vs. 23.8%, p=0.006).  Among patients with RV dysfunction at baseline, an increased RVFAC at the three-month follow-up was associated with a significantly lower risk of the endpoint (aHR [95% CI], 0.35 [0.14-0.89], p=0.028).  However, for patients with normal RV function at baseline, an increase in the RVFAC did not alter the likelihood of mortality or hospitalization for HF.  In addition, patients with a low RV–pulmonary artery coupling (defined as TAPSE/sPAP<0.317 mm/mmHg) and reduction in the TAPSE at the three-month follow-up had the highest risk of the endpoint (aHR, [95% CI]: 5.37 [2.12-13.61], p<0.001).  A logistic regression analysis was conducted to identify predictors of RV responders.  In a small sample of patients with RV dysfunction at baseline (n=45), RV responder was predicted by a smaller RV diameter and a greater reduction of TR severity (aOR [95% CI]: 0.89 [0.80–0.99], p=0.038; and 1.75 [1.07–7.68], p=0.037; respectively) (Tanaka et al., 2024).

Vogelhuber et al. conducted a Bonn registry study of 262 patients to compare outcomes for patients with normal RV function and RV dysfunction.  No differences were revealed between the two groups for the primary endpoint, which was 30-day mortality (RV function, [3.2%] vs. RV dysfunction, [2.3%], p=0.99).  There were also no differences between the two groups for the secondary endpoints of implant success, procedural success, TR reduction of 2 or more grades, in-hospital mortality, or complications (all p > 0.05).  However, at two years, the normal RV function group had improved outcomes in comparison to the RV dysfunction group for mortality (27.0% vs. 56.3%, respectively, p<0.001), cardiovascular death (14.1% vs. 39.0%, p<0.001), and rehospitalization for HF (29.9% vs. 49.1%, p=0.007).  Following T-TEER, RV function declined in the normal RV function group (RVFAC mean [SD], n=205: 46.2 [8.1] vs. 40.3 [9.7], p<0.001), but not in the RV dysfunction group (RVFAC mean [SD], n=41: 29.6 [4.1] vs. 31.6 [8.3], p=0.14) (Vogelhuber et al., 2024).

Stolz et al. conducted a multi-center registry study of 962 patients in Germany.  The authors examined the generalizability of TRILUMINATE Pivotal by applying the trial’s inclusion/exclusion criteria to a real-world cohort and examining the outcomes after one-year post-procedure.  Overall, 54.8% of the patients met the inclusion/exclusion criteria; those meeting the criteria had better left ventricular function and fewer comorbidities than the ineligible group.  For the primary endpoint of one-year survival, the results were significantly higher for the eligible group than the ineligible group (84.7% vs. 74.9%, log-rank p<0.001).  Regarding the secondary endpoint, the eligible group was also significantly more likely to be free from TV surgery, repeat intervention, and hospitalization for HF (72.9% vs. 58.0%, p<0.001) (Stolz et al., 2024).

Publications reporting on the use of PASCAL

Kodali et al. reported the one-year results from the CLASP TR EFS (Edwards PASCAL Transcatheter valve repair system in tricuspid regurgitation Early Feasibility Study).  This study enrolled 65 U.S. patients in a prospective, multicenter, single-arm registry to evaluate the performance and safety of the PASCAL and PASCAL Ace T-TEER systems (Edwards Life Science, Irvine CA).  Thirty-day clinical outcomes were favorable (death, 3.1%; stroke, 1.5%; and no device-related reinterventions), and single leaflet device detachment occurred in three patients (4.6%) within the first month.  At one year, freedom from all-cause mortality and HF hospitalization were 88% and 78%, respectively.  Major bleeding was noted in six patients (9.2%), unplanned reintervention was required in one patient (1.5%), and stroke occurred in three patients (4.6%).  Treatment with T-TEER was associated with improvements in one-year NYHA functional class (92% achieved NYHA functional class I or II; p<0.001 vs baseline), 6MWD (+94 m; p=0.014), and health status or QOL (KCCQ, +18 points; p<0.001).  HF hospitalizations were reduced by 56% in the year following treatment vs. the year before treatment.  Reductions in TR were durable at one year, with 86% of patients having moderate TR or less and all patients achieving at least a one-grade reduction from baseline.  Despite evidence of favorable RV remodeling (i.e., reduced RVEDD and volume), measures of RV systolic function remained unchanged (Kodali et al., 2023).

Wild et al. reported the one-year results from the PASCAL for Tricuspid Regurgitation – a European registry (PASTE) study.  The study included 1,059 patients with severe TR across 16 European heart valve centers that were treated with the PASCAL or PASCAL Precision T-TEER system (Wild et al., 2025).  A significant improvement in NYHA functional class occurred after one year (66% achieved NYHA class I or II vs. 17% at baseline; p<0.001), with 87% of patients having their TR reduced to moderate or less.  All-cause mortality and HF hospitalizations were reported as 14% and 16%, respectively.  While significant improvements in 6MWD (+40 m; p<0.001) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (-9 points; p<0.001) were observed, these outcome parameters were only available in a small subset of patients.

ix.              Limitations of Evidence

The literature for T-TEER is limited and largely represents the European experience.  The pivotal RCT, TRILUMINATE Pivotal, along with the TRILUMINATE Single Arm, Tri.Fr Randomized Clinical Trial, uncontrolled observational studies, and registry-based analyses from Europe represent the extent of the literature on this technology.

The evidence reviewed had several important limitations.  The evidence is inadequate to fully assess which characteristics of the patient, practitioner, or facility predict the most successful patient outcomes from the T-TEER device.

Patients in the trials had various underlying causes of TR.  Due to small sample sizes, subgroup analysis based on TR etiology is not possible, limiting understanding of the benefit of the intervention for specific pathophysiologic entities and disease phenotypes.  Lack of standardization of OMT in the trials was partially an artifact of the many underlying causes of TR.  Improvement in health outcomes following T-TEER for each phenotype cannot be assessed in comparison to OMT for TR in this circumstance.

As there are not accepted criteria to guide which patients benefit from TV intervention, analysis of factors including severity of TR, underlying etiology, measures of cardiac remodeling, degree of hepatic and renal dysfunction, and relationship of TR improvement to morbidity and mortality are necessary to establish whether T-TEER is reasonable and necessary for specific subgroups of Medicare beneficiaries.

The identified limitations of the reviewed published studies are summarized in the following evidence deficiencies:

  • Studies with larger sample sizes are needed to identify and reliably demonstrate which Medicare beneficiaries are likely to benefit from T-TEER and how that benefit varies by subgroup.  Specifically, more evidence is needed for:
    • Patients with greater than mild RV dysfunction and those with hepatic or renal dysfunction;
    • Subpopulations defined by sex, age, other demographic characteristics, and important comorbidities;
  • Durability and treatment benefit for hospitalization, total hospitalizations, or survival should be demonstrated for at least two years;
  • One or more objective clinical outcomes, especially mortality, should be demonstrated for at least two years;
  • More evidence is needed to identify which implant size of the TriClip device is most appropriate for specific patients;
  • More evidence is needed to define the optimal coaptation gap for successful T-TEER;
  • More evidence is needed to define the treatment conditions (e.g., implanting physician experience/training, echocardiographer experience/training, heart team, facility characteristics) necessary to achieve optimal T-TEER outcomes;
  • Given the high risk of bias inherent in unblinded studies, T-TEER studies should pre-specify both subjective (e.g., QoL, functional outcomes) and objective (e.g., HF hospitalization, HF hospitalization or HF hospitalization equivalent events, total hospitalizations, survival) outcome criteria;
  • In composite outcome measures all outcomes comprising the composite outcome should demonstrate movement in the same direction (e.g., physiologic, patient-reported, and other relevant health outcomes).

Patients enrolled in TRILUMINATE Pivotal and in Tri.Fr had a mean age of 78 years; however, there are limits in extrapolating trial results to the broader pool of Medicare beneficiaries eligible for T-TEER.  TRILUMINATE Pivotal, TRILUMINATE Single Arm, and Tri.Fr were trials conducted on select populations with stringent inclusion and exclusion criteria and patients were assessed, treated, and managed in highly controlled settings. This is a common limitation of RCTs, and larger, real-world, registry-based studies can provide the generalizability we seek to Medicare beneficiaries in their usual care settings.

The reviewed observational studies included a broader diversity of patient characteristics and treatment settings.  The mean age of the observational studies ranged from 75 to 82 years.  Single-center studies included in this review may not adequately represent the varied experience levels of providers conducting T-TEER procedures in general use.  Additionally, many of the included studies were conducted outside of the US, which limits the applicability of outcomes such as hospitalization that may be influenced by differences in insurance and health system factors.

x.                Considerations for Further Research

CMS maintains an interest in monitoring important health outcomes to better inform our understanding of the risk/benefit profile, particularly for subpopulations, as coverage for T-TEER is considered for the treatment of symptomatic tricuspid regurgitation.

To better serve Medicare beneficiaries, additional evidence should address:

  1. Sufficient patient enrollment to have confidence that expected outcomes will be reliably achieved in real-world use;
  2. Sufficient representation of Medicare beneficiaries, disease subgroups, and demographic groups in clinical studies of the TriClip device to demonstrate generalizability to those populations;
  3. Clinical studies of sufficient duration to demonstrate that observed outcomes demonstrate clinically meaningful differences and are durable to an extent appropriate for treatment of tricuspid regurgitation;
  4. Clinical studies clarifying the site of service, clinical staffing, and experience profiles associated with expected outcomes in real-world use of transcatheter edge-to-edge repair of the tricuspid valve.

Based on the evidence review, we believe that evidence published in the peer reviewed literature should critically evaluate the following outcomes through a minimum of one year:

  • Exercise capacity measures (6MWD);
  • Functional assessments as meaningful primary health outcomes within a composite outcome.

CMS believes that evidence published in the peer-reviewed literature should critically evaluate one or more of the following outcomes through a minimum of two years:

  • For right HF or severe TR, surrogate or intermediate endpoints (e.g., need for re-intervention or replacement of the tricuspid valve; complications related to right heart pacing);
  • HF hospitalization;
  • HF hospitalization equivalent events;
  • Total hospitalizations;
  • Total mortality;
  • Survival.
F.               Evidence-Based Guidelines

We identified two professional society guidelines relevant to the contemporary care of patients with TR.  Both guidelines focus on appropriate medical and surgical care of the TR patient.

European Society of Cardiology (ESC) / European Association for Cardio-Thoracic Surgery (EACTS) Guidelines 2021 (Vahanian et al., 2022):

  • In primary TR, “surgery should be considered in asymptomatic or mildly symptomatic patients with isolated severe primary tricuspid regurgitation and RV dilatation who are appropriate for surgery.(IIa)”
  • In secondary TR, “surgery should be considered in patients with severe secondary tricuspid regurgitation (with or without previous left-sided surgery) who are symptomatic or have RV dilatation, in the absence of severe RV or LV dysfunction and severe pulmonary vascular disease/hypertension.”
  • “Transcatheter treatment of symptomatic secondary severe tricuspid regurgitation may be considered in inoperable patients at a Heart Valve Centre with expertise in the treatment of tricuspid valve disease.” Transcatheter treatment “may be considered by the Heart Team at experienced Heart Valve Centers in symptomatic, inoperable, anatomically eligible patients in whom symptomatic or prognostic improvement can be expected.”
  • In patients with bioprosthetic failure, transcatheter valve-in-valve implantation in the tricuspid position “may be considered in selected patients at high-risk for surgical reintervention.”

American College of Cardiology (ACC) / American Heart Association (AHA) Joint Committee on Clinical Practice Guidelines 2020 (Otto et al., 2021):

  • “In appropriately selected symptomatic patients with AF-related severe TR, quality of life and symptoms can be improved by surgical intervention for TR.  In patients undergoing intervention, overall outcomes are better in those without severe RV dysfunction or end-organ damage.”
  • “Correction of symptomatic severe primary TR (Stage D) in patients without left-sided valve disease would preferentially be performed before the onset of significant RV dysfunction or end-organ damage. Randomized studies of early intervention are lacking, and the benefit might be limited by the risk of intervention, suboptimal reduction in TR severity, or suboptimal durability of currently available approaches to tricuspid valve repair and replacement.”
  • “In patients with signs and symptoms of right-sided HF and severe isolated secondary TR attributable to annular dilation (in the absence of pulmonary hypertension or left-sided disease) who are poorly responsive to medical therapy (Stage D), isolated tricuspid valve surgery can be beneficial to reduce symptoms and recurrent hospitalizations. (2a)”
  • “In asymptomatic patients with severe primary TR (Stage C) and progressive RV dilation or systolic dysfunction, isolated tricuspid valve surgery may be considered. (2b)”
  • “In patients with signs and symptoms of right-sided HF and severe TR (Stage D) who have undergone previous left-sided valve surgery, reoperation with isolated tricuspid valve surgery may be considered in the absence of severe pulmonary hypertension or severe RV systolic dysfunction. (2b)”
  • The guideline does not address transcatheter tricuspid valve interventions.
G.             Professional Society Recommendations / Consensus Statements / Other Expert Opinion

We identified five relevant professional consensus documents.  These provide context for the standard of care in managing TR.

Scientific Statement from the American Heart Association 2024 (Davidson et al., 2024)

  • Use of the 5-grade scale (mild, moderate, severe, massive, and torrential) for reporting of TEE “allows a more specific classification of TR that is severe or greater.”
  • “At present, there are no guidelines to determine whether an individual patient may be better suited for transcatheter TV repair or replacement.”
  • “It is…also important to consider the lifetime management of patients with TV disease.  When a young patient presents with severe TR, they will need a durable device and ideally the potential option of a second transcatheter device in the future should the first device deteriorate over time…For an elderly, frail patient, alleviating symptoms and improving their present quality of life may be the primary goal; therefore, long-term lifetime management may not be as applicable.  As clinical studies continue, a greater understanding of device durability will allow clinicians to better advise patients about the long-term management of TV disease.”
  • “For patients with large annuli due to RV failure, atrial fibrillation, or a combination, tricuspid TEER may be difficult, if not impossible, because of large coaptation gaps.  These patients may be better suited for transcatheter TV replacement or transcatheter annuloplasty.”
  • Severity of pulmonary hypertension (PH) should be considered in treatment choice due to risks of “complete and sudden elimination of TR in patients with severe PH leading to acute RV failure and hemodynamic instability.”
  • The presence of CIED leads may inform choices about transcatheter TV therapy.  The location of leads may interfere with device placement and device choice may impact future pacemaker options.

A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology 2024 (Adamo et al., 2024)

  • “Notably, there are no specific drugs (i.e. neurohormonal modulators) shown to have beneficial effects on the symptoms, clinical course and prognosis of patients with RHF and TR.  Current guidelines clearly state that medical therapy (i.e. diuretics) should not delay TR intervention when indicated.”
  • “Recently, a dedicated risk model, the TRI-SCORE, was proposed to estimate in-hospital mortality in patients undergoing isolated TR surgery.  Notably, most of the variables included in this model (age ≥70 years, NYHA functional class III–IV, right-sided HF signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 ml/min, elevated total bilirubin, LVEF <60%, moderate/severe RVD) are HF- and congestion-related confirming the prognostic importance of HF stage and presentation.”
  • “Further randomized controlled studies, including more symptomatic patients and correctly powered for hard endpoints and with long follow-up are urgently needed to clearly understand whether TR correction may improve prognosis in these patients in addition to the benefit in quality of life.”

Tricuspid regurgitation management: a systematic review of clinical practice guidelines and recommendations (Ricci et al., 2022)

  • “There is consensus on definition of TR severity, utility of multimodality imaging and right heart catheterization, management of symptomatic and asymptomatic TR, choice of surgical techniques, and indications for conservative management.”
  • “Gaps in evidence include: TTVI indications, endpoint definition for TTVI, risk assessment models, indications for minimally invasive tricuspid valve surgery.”
  • “Pending results of RCTs of TTVI, currently only the European guidelines makes (sic) a weak, class IIb indication for the use of transcatheter treatment of TR in symptomatic, inoperable, and anatomically eligible patients, in whom symptomatic or prognostic improvement can be expected according to evaluation by the heart team.”
  • “The clinical efficacy of TTVI and optimal candidate profile are yet to be delineated, and will need to be tested in randomized controlled trials.  The current evidence is limited to small numbers of patients, but demonstrates a favourable safety profile and improvement in clinical symptoms.”

Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review (Chang et al., 2020)

The review emphasized that clinical data on most of the devices are not sufficient to draw conclusions about their safety and efficacy.  They recommended that when evaluating the early clinical data, the following issues should be addressed: “(1) Patients enrolled in first-in-man studies differ markedly in terms of TR severity, EROA, vena contracta area, with some studies focusing on severe TR as compared to torrential TR.  This must be considered when efficacy in TR reduction and potential for clinical improvements of different devices/approaches are assessed. (2) General application and comparison between studies are hindered by the differences in study design. (3) Clinical and echocardiographic endpoints, device, and procedural success, and optimal TR reduction should be clearly defined. (4) Most of the surgical data on the TV are derived from patients who underwent left-sided heart surgery which is not fully transferable to dedicated transcatheter interventions.”

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints (Hahn et al., 2023)

The Tricuspid Valve Academic Research Consortium (TVARC) has published guidance on meaningful efficacy endpoints in trials of tricuspid valve interventions.  As part of the TVARC analysis, the authors identified important knowledge gaps, including around how to stratify patient outcomes, value of the extended TR severity grading scale, how to define OMT in TR, how to define risk of adverse outcomes with different management strategies, and how to determine patient selection, goals of therapy, and clinically meaningful outcomes for transcatheter device therapies.  The goal of defined trial endpoints is to facilitate closure of these knowledge gaps.

Endpoints of value that were highlighted were all-cause mortality as the primary mortality endpoint; reporting of all-cause hospitalization as well as CV and HF hospitalizations, including whether valve or procedure related; and reporting of “heart failure hospitalization equivalent” events, which include aggressive outpatient management of HF exacerbations.  The Consortium recommended adjudicating cardiovascular mortality as a secondary outcome and asserted that procedure or device relatedness should be reported.  Patient-centered outcomes were considered important, but the authors highlighted the placebo effect inherent in the use of KCCQ, acknowledging up to 10-12 point improvements seen in the control arms of HF trials.  For functional outcomes, a 25-50 m increase in 6MWD was described as clinically significant, depending on functional level at baseline.

Regarding imaging endpoints, the authors acknowledge the shortcomings of quantitative methods in echocardiography following device implantation and advocate for development of consensus algorithms for post-intervention imaging.  Included in imaging parameters were cardiac output, hepatic vein flow reversal, and measures of RV function and RV-PA coupling, and the authors stated that studies on reverse remodeling following TV intervention have reported conflicting results.  Finally, the authors addressed biomarkers and end-organ function as important endpoints.  Natriuretic peptide levels, reduction in septal shift, and CA 125 may be good indicators of cardiac function, and markers of liver and renal function may improve with reduced congestion.  Biomarkers recommended as endpoints were included in the document.

The guidance document also addressed important safety endpoints, including TV reintervention, bleeding, injuries (vascular, access-related, and cardiac), conduction disturbances and complications involving CIEDs, neurological events due to paradoxical emboli, PE/DVT, and acute kidney injury.  The authors made an important distinction between device- and procedure-related complications, providing guidance on how to adjudicate and report and acknowledges differences in expected complications between repair and replacement procedures, advocating for use of the TVARC definitions by clinical events committees for objectivity and consistency.

Finally, measures of success were outlined for both the short- and long-term.  Intraprocedural success was defined as successful device deployment and satisfactory immediate performance of the device, without serious complications.  Clinical success was defined as correct positioning of the device with adequate function, without procedure related complications, need for reintervention, or readmission for TR.  Additionally, clinical success at ≥ 30 days incorporates valve performance, MAE, clinical outcomes, functional status, and QoL.  The authors acknowledge an intent to simplify success endpoints compared with mitral valve criteria for ease of implementation.

H.              Appropriate Use Criteria

There are no relevant, published appropriate use criteria.

I.                  Public Comment

CMS uses the initial public comments to inform its proposed decision.  Public comments that cite published clinical evidence give CMS useful information.  Public comments that contain 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.

First Comment Period: October 3, 2024 – November 2, 2024

During the first 30-day public comment period CMS received 64 comments.  The majority of commenters spoke positively of the use T-TEER.  A few commenters did not support coverage of T-TEER because of limited evidence.  All comments that were submitted during the comment period without personal health information may be viewed by using the following link: https://www.cms.gov/medicare-coverage-database/view/ncacal-public-comments.aspx?ncaId=316&fromTracking=Y& Opens in a new window.

The majority of comments were anecdotes provided by physicians who utilized T-TEER among their patients.  Three comments were received from medical technology manufacturers, including Abbott, Boston Scientific, and Edwards Lifesciences.  We received one joint comment from the American Association for Thoracic Surgery (AATS), the American College of Cardiology (ACC), the American Society of Echocardiography (ASE), the Heart Rhythm Society (HRS), the Society for Cardiovascular Angiography and Interventions (SCAI), and the Society of Thoracic Surgeons (STS).  One comment was received from a trade association, the Medical Device Manufacturers Association (MDMA).  One comment was received from a patient advocacy organization, Heart Valve Voice US.  One comment was received from a group of clinician and patient advocacy organizations, the Heart Valve Disease Policy Task Force.

Second Comment Period: April 3, 2025 – May 3, 2025

During the second 30-day public comment period CMS received 30 comments.  Of these comments, one comment that was not pertinent to T-TEER was omitted from publication on the CMS website, for a total of 29 comments posted to the CMS website.  Similar to the initial public comment period, the majority of commenters spoke positively of the use of T-TEER and the proposed coverage.  A few commenters did not support coverage of T-TEER because of limited evidence.  All pertinent comments that were submitted during the comment period without personal health information may be viewed by using the following link: https://www.cms.gov/medicare-coverage-database/view/ncacal-public-comments.aspx?ncaId=316&fromTracking=Y& Opens in a new window.

Additionally, the majority of comments were anecdotes provided by physicians, many of whom utilized T-TEER among their patients.  We received one comment from Mayo Clinic. We received three comments from medical technology manufacturers, including Abbott, Boston Scientific, and Edwards Lifesciences.  One comment was from an industry organization, the Advanced Medical Technology Association (AdvaMed).  We received two comments from professional associations, including one from the Association of Black Cardiologists (ABC) and a joint comment from the American Association for Thoracic Surgery (AATS), the American College of Cardiology (ACC), the American Society of Echocardiography (ASE), the Heart Rhythm Society (HRS), and the Society of Thoracic Surgeons (STS).  One comment was from a group of clinicians and patient advocates, the Heart Valve Disease Policy Task Force.  One comment was from a health research advocacy organization, the National Center for Health Research.  One comment was from the University of California San Francisco (UCSF) Team for High-Value Care.  We received one joint comment from Novitas Solutions, Inc. and First Coast Service Options, Inc.  We received one comment from the American Heart Association (AHA), including the American Stroke Association (ASA).

1.                Support for Medicare Coverage for T-TEER

Comment:  The majority of commenters expressed support for the use of T-TEER.  Some of these commenters emphasized that they would expect T-TEER to improve quality of life and reduce symptoms of TR.

Response:  We thank commenters for their support.

Comment:  The majority of commenters expressed general support for Medicare coverage of T-TEER. Many commenters shared positive anecdotes about patients who had received this device.

Response:  CMS appreciates these thoughtful comments.  We thank all of the clinicians and advocates that shared their experiences.

Comment:  Many commenters expressed support for the heart team approach in the care and treatment of TR.

Response:  We thank commenters for their support.

2.                Non-Coverage for T-TEER

Comment:  A couple of commenters did not support coverage for T-TEER for various reasons.  These commenters stated that T-TEER has not shown clinically meaningful benefit and noted they were concerned that the TRILUMINATE Pivotal trial did not show a decrease in mortality, tricuspid valve surgeries, or overall hospitalizations with T-TEER compared to medical therapy.  They also expressed concern over the rates of adverse events, the rate of crossover from the medical therapy group to the T-TEER group, and potential placebo effects due to unblinding.

Response:  We recognize the concerns that commenters have raised and have taken them into consideration as we finalized this decision.  While we agree that there are evidence gaps that still need to be addressed regarding T-TEER, we believe the evidence overall, while insufficient, is promising enough to allow coverage with evidence development (CED).  The primary outcomes described in the CED criteria are all-cause mortality and hospitalizations through a minimum of 24 months.  The final NCD includes CED study criteria that strike the appropriate balance between evidence generation and patient access.

3.                Coverage Indications

Comment:  Some commenters recommended specific definitions of OMT for patients prior to T-TEER.

Response:  Due to potential variability in the definition of OMT across guidelines, CMS is finalizing the patient criteria as proposed to allow flexibility for practitioners to determine the appropriate medical management for each patient.  We note that specific decisions regarding OMT are often guided by cardiologists with training and experience in HF management.

Comment:  One commenter recommended coverage for symptomatic severe TR to align with the FDA’s approved premarket approval application for TriClip and the TRILUMINATE Pivotal trial.  This commenter also recommended including signs such as liver congestion and peripheral edema refractory to medical therapy in this condition severity.

Response:  We appreciate this comment.  We are finalizing the coverage indications without specifying TR severity.  We note the final NCD criteria are consistent with the current FDA-approved label and will continue to align with FDA labeling for symptomatic TR if indication language on severity is updated.

4.                Physician Criteria

Comment:  One commenter requested clarification on whether every patient must consult with every member of the heart team.

Response:  We appreciate this comment.  While the final NCD specifies the minimum membership of the heart team, it does not specify the role of each heart team member.  As part of the CED requirements for this NCD, CMS requires that the study sponsor establish a care management plan that includes the experience and role of each member of the heart team, but does not require that every patient must consult with each member of the heart team.

Comment:  Several commenters recommended removal of the requirement for the heart team to include an electrophysiologist.  One commenter stated that the risks of conduction disturbances, heart block, and pacemaker implantation after T-TEER are low.  This commenter stated that the evidence does not support requiring an electrophysiologist to evaluate the likelihood of procedural success or for rapid access during T-TEER procedures.  Several commenters stated that an electrophysiologist can be consulted if needed but should not be required on the heart team.  A few commenters stated that requiring an electrophysiologist could increase burden and delays and limit access to T-TEER.  One of these commenters noted that there are other structural heart procedures with known conduction risks that do not require electrophysiology consultation.

Response:  We agree that consultation with an electrophysiologist may be appropriate in specific cases, but should not be required for every procedure.  We have revised the final decision language to remove the requirement for an electrophysiologist on the heart team. 

Comment:  A couple commenters requested clarification on whether the same individual can satisfy the requirements for an “Interventional echocardiographer” and “Multi-modality imaging specialists” on the heart team.  One of these commenters noted that echocardiogram is currently the primary imaging modality for T-TEER.  Another commenter stated that T-TEER procedures should include an interventional echocardiographer, which is different from a multimodality imager.  One commenter recommended that T-TEER procedures should be performed by at least two physicians working as co-operators, including an interventional echocardiographer providing imaging expertise during all aspects of the procedure, and an interventional cardiologist or cardiac surgeon providing expertise in wire, catheter, and device manipulation and deployment.  One commenter stated that the role of the imaging specialist and/or the interventional echocardiographer should not be considered as mandatory and that imaging may be done expertly by the HF cardiologist, the interventional cardiologist, or the cardiac surgeon. 

Response:  We appreciate these thoughtful comments.  We agree with commenters who stated that an interventional echocardiographer must be on the heart team.  We recognize that echocardiogram is the primary imaging modality for T-TEER and have revised the final decision language to remove the requirement for multi-modality imaging specialists on the heart team.  The final physician criteria allows flexibility for heart teams to consult other multimodality imaging specialists based on the imaging modalities that are clinically appropriate for each patient.

Comment:  One commenter recommended additional measures for pre-procedural planning, including cardiac computed tomography (CT) to assess tricuspid valvular anatomy and invasive hemodynamic assessment of volume status, TR, and RV function.  The commenter also recommended that T-TEER be performed when a patient is optimally diuresed.

Response:  We appreciate the comment.  We recognize that advanced imaging, beyond echocardiography, may be appropriate for some patients to ensure a complete understanding of the anatomy and function of the tricuspid valve to properly assess appropriateness and feasibility of T-TEER.  As part of the CED requirements for this NCD, rather than CMS including stringent criteria, CMS requires that the study sponsor establish a care management plan that includes the experience and role of each member of the heart team.  Overall, care pathways should be clarified in the care management plan and CMS anticipates these will include appropriate pre-procedure evaluation and medical optimization of the patient considered for T-TEER.

Comment:  A couple of commenters stated that T-TEER teams should be similar to mitral TEER.  One commenter also stated that T-TEER should be performed by at least two physicians working as co-operators, including an interventional echocardiographer to provide imaging expertise and an interventional cardiologist or cardiac surgeon to provide expertise in wire, catheter, and device manipulation and deployment.

Response:  We appreciate these comments.  While the NCD discusses the membership of the heart team, it does not specify which operators should be involved in the procedure.  As part of the CED requirements specified in this NCD, rather than CMS dictating which operators should be involved in the procedure, CMS requires that the study sponsor establish a care management plan that includes the experience and role of each member of the heart team.

5.                Institutional Criteria

Comment:  Some commenters stated that T-TEER should be performed in centers that currently provide certain therapies, such as mitral TEER and transcatheter aortic valve replacement (TAVR).  Some commenters supported facility volume requirements for initiation and maintenance of T-TEER programs and recommended specific personnel and resources that should be required within the hospital program.

Response:  CMS appreciates these comments.  At this time, the evidence is insufficient to include specific facility procedural volume or resource requirements for T-TEER programs, and we decline to include such requirements in this final decision. A study sponsor has flexibility to add facility procedural volume or resource requirements in its protocol if they choose.

6.                Volume Criteria

Comment:  A few commenters recommended minimum procedural volume requirements for physicians and hospital programs performing T-TEER procedures.  One commenter suggested that volume requirements are necessary to optimize and maintain outcomes. 

Response:  We appreciate these thoughtful comments.  CMS believes the available evidence does not currently support specific volume requirements for physicians or hospital programs performing T-TEER procedures.  CMS is finalizing this NCD with CED study criteria that encourage generation of peer-reviewed literature on the practitioner and facility level variables that predict study outcomes.

Comment:  Some commenters expressed concern that volume requirements would limit the availability of T-TEER and restrict care.  One commenter stated that experienced structural teams performing transcatheter therapies should not be dependent on the surgical team's mitral valve surgical experience.  Another commenter asserted that volume is not a proxy for quality and noted that several analyses have found no significant difference in outcomes between high- and low-volume TAVR centers.  Another commenter supported deferring inclusion of experience requirements to when CED data are available to inform the decision.

Response:  The final NCD does not include volume requirements.  CMS believes the final NCD includes CED study criteria that strikes an appropriate balance between evidence generation and patient access.

7.                CED Criteria for T-TEER

Registry

Comment:  A few commenters supported collection of T-TEER data through registry participation.  One commenter stated that mandatory registry participation will facilitate post-market surveillance, long-term outcome measurement, and comparative effectiveness research.  One commenter recommended aligning coverage with mitral TEER by using national registry participation as a mechanism for continued evidence generation. 

Response:  We appreciate these comments.  As discussed in the analysis of evidence gaps, evidentiary gaps remain regarding T-TEER outcomes for certain patient subgroups and regarding the operator, facility, and procedure team characteristics that can replicate or exceed trial results.  The purpose of CED is to address these evidence gaps.  The final NCD criteria do not preclude coverage of a registry-based study of T-TEER if that study satisfies the requirements of the NCD and the study protocol has been reviewed and approved by CMS.  We note that registry participation post-market may be required in FDA post-approval studies.

Outcomes

Comment:  Some commenters suggested parameters for a high-quality study as part of CED, including study design features and endpoints.  These commenters recommended follow-up through five years, with analyses conducted each year.

Response:  We appreciate these comments.  We strive to strike an appropriate balance between reducing burden on providers and obtaining necessary data to inform future coverage determinations.  We believe multi-year follow-up data is crucial to the development of evidence for this topic.  It is for this reason the CED criteria include requirements for studies to report the primary outcomes for a minimum of 24 months.  As typically done in studies, we anticipate that CED study protocols may have provisions for following patients past the 24-month period specified as the minimum needed for the primary analysis.

Active comparator

Comment:  One commenter expressed concern regarding active contemporaneous comparators in the study design.  This commenter noted limitations of certain data sources and the potential for bias in study results.

Response:  The active comparator design potentially helps to reduce both measured and unmeasured confounding.  A study design without an active comparator will typically not be considered fit-for-purpose by CMS, except in unusual circumstances where the conditions for single-arm study credibility are met, and the construction of a control group is not feasible.  In observational study designs, randomization is not used, but various methods (e.g., propensity matching, use of instrumental variables) may be employed to simulate randomization and construct an active comparator that minimizes the potential for bias/confounding.

Subgroup analyses

Comment:  One commenter requested that CMS remove “advanced” from the subgroup analysis of “advanced hepatic dysfunction,” since there is no standard clinical definition of “advanced” hepatic dysfunction.

Response:  We appreciate this thoughtful comment.  We have revised the final decision language to remove the specification of “advanced” hepatic dysfunction.  The final CED study criteria require protocols to discuss how “hepatic dysfunction” will be defined and studied.

Comment:  One commenter recommended subgroup analyses in addition to what has been proposed, such as mechanism of TR, frailty, and comorbidities.

Response:  CMS considers many subgroups to be of importance in generating a thorough understanding of which patients derive the most benefit from and, potentially, which patients may be harmed by T-TEER.  We explain in this final decision memo that a CED study would be considered successful if it demonstrated “Specific patient and disease phenotype subgroups likely to benefit from T-TEER.”  We recognize the complexity of TR and patients with TR, as well as the many potential subgroups available for analysis.  CMS encourages generation of peer-reviewed literature, reporting on evidence of health outcomes in subgroups beyond those required by the CED requirements in the NCD.  The universe of available evidence will be assessed for inclusion in any future reconsideration of this NCD and high-quality evidence on relevant subgroups will be helpful to inform a coverage determination.

8.                Miscellaneous Comments

Comment:  One commenter recommended recently published evidence for inclusion in this analysis.  This commenter also noted language in the labeling for the TriClip G4 System that has been removed from the labeling for the TriClip G5 System.

Response:  We appreciate this comment.  We have incorporated recently published evidence into the final decision memorandum.  We note that the updated labeling for the TriClip G5 System is not publicly available from the FDA.  The updated labeling referenced in this public comment does not change the final NCD criteria.

Comment:  One commenter expressed concern that a study sponsor intended to utilize their registry data without their engagement early in the evidence development process.

Response:  This comment is outside of the scope of this NCD.  We note that the collection and use of data by study sponsors must satisfy the requirements in the final NCD.

Comment:  One commenter supported payment that appropriately reflects the contributions of all physicians involved, especially in cases that necessitate multiple intraoperative participants.

Response:  This comment is outside of the scope of this NCD.

Comment:  Two commenters recommended flexibility for approved T-TEER CED studies to be updated and refined throughout the course of the NCD.

Response:  We appreciate these comments.  As with any approved CED study, protocol modifications are possible, but the modifications must fully comply with the NCD requirements and must be reviewed and approved by CMS.

IV.         CMS Coverage Analysis

A.              CMS Coverage Authority

National coverage determinations (NCDs) are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally by Medicare (§1869(f)(1)(B) of the Social Security Act (the Act)).  In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B and must not be otherwise excluded from coverage.  Moreover, with limited exceptions, items or services must be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member (§1862(a)(1)(A) of the Act).

When the available evidence is insufficient to demonstrate that the items and services are reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member under section 1862(a)(1)(A) of the Act, coverage with evidence development (CED) has been used to support evidence development for certain items and services that are likely to show benefit for the Medicare population. [1]  CED has been a pathway whereby, after a CMS and AHRQ review, Medicare covers items and services on the condition that they are furnished in the context of clinical studies or with the collection of additional clinical data.[2]  (See CMS’ CED Guidance Document Opens in a new window.) CED relies primarily on the statutory exception in section 1862(a)(1)(E) of the Act, which effectively permits Medicare payment for items and services that are reasonable and necessary to carry out research conducted pursuant to section 1142 of the Act.

Section 1142 of the Act describes the authority of AHRQ to conduct and support research that appropriately reflect the needs and priorities of the Medicare program.[3]

B.              CMS Analysis for Coverage of T-TEER for TR

1.                Rationale for Coverage Requirements for T-TEER for TR (Patient, Physician, and CED Study Criteria)

The Centers for Medicare & Medicaid Services (CMS) covers transcatheter edge-to-edge repair of the TV (T-TEER) under Coverage with Evidence Development (CED) for the treatment of symptomatic tricuspid regurgitation according to the provisions in sections I.B (Coverage Criteria) and I.C (Other Uses of T-TEER) under the Decision section of this document, which are explained below.

Context of care:

Coverage Criteria

T-TEER is covered when furnished according to a Food and Drug Administration (FDA) market-authorized indication.

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.

These criteria are consistent with the TRILUMINATE pivotal trial inclusion criteria and FDA-approved label indications.

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.

T-TEER Heart Team Composition:  The multi-disciplinary heart team is a patient-centered concept that supports evidence-based medical decision making and promotes the best possible outcomes.  We propose that the heart team provide comprehensive pre-procedural evaluation of a patient’s care options, collaborative peri-procedural care, and post-procedural care until the patient’s outpatient condition is stabilized following T-TEER, allowing for transition to a community cardiologist for routine care. This requirement is consistent with the FDA-approved label for the TriClip system and management of patients with cardiac valvular disorders.  Consensus documents supporting the concept of a heart team include European Society of Cardiology (ESC) / European Association for Cardio-Thoracic Surgery (EACTS) Guidelines 2021, which state, “Decisions concerning treatment and intervention should be made by an active and collaborative Heart Team with expertise in valvular heart disease (VHD), comprising clinical and interventional cardiologists, cardiac surgeons, imaging specialists with expertise in interventional imaging, cardiovascular anaesthesiologists, and other specialists if necessary (e.g. heart failure specialists or electrophysiologists).”

Cardiac surgeon:  CMS recognizes the importance of the cardiac surgeon to the integrity and quality of a transcatheter valve program, as articulated in the 2018 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document: Operator and Institutional Recommendations and Requirements for Transcatheter Aortic Valve Replacement and the subsequent consensus statements on transcatheter valves.  Guidelines on the necessity of surgical consultation and surgeon availability before, during, and following valve procedures have been consistent and are well-accepted in the clinical community.  In the TRILUMINATE Pivotal trial, the cardiac surgeon on the site heart team was required to “concur that the patient is at intermediate or greater estimated risk for mortality or morbidity with tricuspid valve surgery” as an inclusion criterion.  FDA labeling for TriClip G4 specifies that “The TriClip G4 System should be implanted … in a facility with immediate access to cardiovascular surgery.”  Potential need for rescue procedures mandates the inclusion of a cardiac surgeon.

Interventional cardiologist:  Interventional cardiologists are universally recognized as providers of catheter-based structural heart interventions and structural heart interventions are specified in interventional cardiology fellowship training requirements.  European Society of Cardiology (ESC) / European Association for Cardio-Thoracic Surgery (EACTS) Guidelines 2021: “Expertise in interventional and surgical management of coronary artery disease (CAD), vascular diseases, and complications must be available.”

Cardiologist with training and experience in heart failure management:  The TRILUMINATE Pivotal trial required participation of a HF cardiologist in the heart team.  As supported by multiple consensus documents, including the American College of Cardiology (ACC) / American Heart Association (AHA) Joint Committee on Clinical Practice Guidelines 2020, the European Society of Cardiology (ESC) / European Association for Cardio-Thoracic Surgery (EACTS) Guidelines 2021, and A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology 2024, right heart catheterization (RHC) can be critical to the decision-making of the heart team.  Diagnostic RHC is often performed by cardiologists with training and experience in HF management as part of comprehensive management of patients with complex HF.  These recommendations underscore the importance of attentive, expert medical management of patients with TR by HF specialists familiar with the complexities of TR.

Interventional Echocardiographer:  We are specifying a need for expertise in interventional echocardiography due to the complexity of visualization of the tricuspid valve and the need for continuous echocardiographic guidance during placement of the transcatheter tricuspid valve.  Literature in support of this complexity and supporting this requirement can be found in the ESC/EACTS guideline, which establishes a requirement that “intraprocedural transesophageal echo, preferably 3D, is used to guide transcatheter mitral and tricuspid valve procedures and to assess the immediate result of surgical valve operations.  The guideline supports use of the 5-level grading system…”  The American Society of Echocardiography has published a guideline outlining competencies for echocardiographic guidance of structural heart disease endorsed by the Society of Cardiovascular Anesthesiologists and multiple international echocardiography societies, that describes the tricuspid valve as “more difficult to image than the mitral valve” and endorses and describes requirements for level III interventional echocardiography (Little et al., 2023).  FDA labeling for TriClip G4 specifies that “The TriClip G4 System should be implanted … using fluoroscopy and transoesophageal echocardiography” and that “Echocardiographic images should be carefully assessed to ensure they are of adequate quality to allow successful implantation of the TriClip G4 Implant.”

3. Coverage with Evidence Development

CMS acknowledges limitations in the published evidence available to assist the heart team in optimal patient selection for T-TEER.  Because evidentiary gaps remain relative to optimization of patient selection for T-TEER, CMS will carefully monitor and assess patient outcomes during CED and through evidence published in the peer-reviewed literature.

All CMS-approved CED studies must meet the patient and physician criteria above and include:

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.

Rationale for (a):
All-cause mortality is a core patient-centered outcome that accounts for competing causes of death without further adjudication and appears in composite primary outcomes of reviewed trials along with HF hospitalizations.  In their endpoints guidance (Hahn et al., 2023), the TVARC prioritized all-cause mortality in studies of transcatheter valves due to the observation of death from non-cardiac sequelae of TR, such as hepatic and renal disease.  The endpoints guidance also prioritizes all-cause hospitalization as well as CV and HF hospitalizations.

The 24-month minimum period for CED studies expands evidence for durability of outcomes beyond past trials.

Each component of a composite outcome must be individually reported to assess which component(s) is(are) driving the outcome.  For example, if a substantial reduction in a composite of all-cause mortality and HF hospitalizations were driven by the latter, and mortality actually increased slightly, that benefit (substantially decreased hospitalizations) and harm (slightly increased mortality) would be important for physicians and patients to know when making decisions.

b)      An active comparator.

Rationale for (b):
Benefits and harms cannot be assessed without a comparator.  An “active comparator” is inherent in RCTs that prospectively compare randomized intervention and control groups, but may be seen in other study designs, such as those employing propensity-score matching or instrumental variables.  The latter studies can be many times larger than RCTs, and we believe can help fill in evidence gaps, especially for subgroups, left in the wake of the foundational but limited studies of T-TEER.

c)      A care management plan that includes the experience and role of each member of the heart team described in section I.B.2 and IV.B.1.

Rationale for (c):
The trials that generated the promising evidence for T-TEER were performed in highly-specialized medical centers with expertise at transcatheter valve intervention.  Insufficient data are available on the selection criteria for centers and operators utilized in the trials, and the randomized trial utilized a roll-in period prior to randomization of patients to develop competency in the performance of the procedure.  Active data collection on treatment conditions, including operator, facility, and procedure team characteristics, is needed in CED studies to understand conditions that can replicate or exceed those trial results.  The entire care plan that details the experience and role of each member of the heart team, as well as patient outcomes stratified by operator and facility characteristics, developed by study investigators and embedded in CED study protocols, would provide an evidence-based roadmap for real-world clinical care after CED studies are completed.

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.

Rationale for (d):

More evidence is needed about the above subgroups to determine which patients will clinically benefit from, or be harmed by, T-TEER, and under what treatment conditions and the practitioner and facility level variables.  Note that patients with LVEF ≤ 20%, any prior TV procedure that would interfere with placement of the device, indication for mitral, aortic or pulmonary valve correction (untreated), CIED leads that would interfere with placement of the device, and patients on dialysis were excluded from the RCT.  We do not exclude these patients from CED studies, but instead require subgroup analysis of them, because these are core Medicare subpopulations or subpopulations with symptomatic TR.  Further, the 2024 American Heart Association Scientific Statement on valvular disease asserts, “the presence of CIED leads may inform choices about transcatheter TV therapy for each individual.  It must be understood how the location of the leads may or may not interfere with device placement and what pacemaker options will be available to the patient in the future once a transcatheter TV device is in place.”  Understanding complications and outcomes in patients with CIEDs following T-TEER is necessary to guide appropriate therapy in this group of patients with TR.  Recent observational evidence suggests that, as with mitral valve repair, degree of residual TR after repair is associated with survival (Stolz et al., 2024).  The TRILUMINATE Pivotal investigators have also asserted the importance of the degree of valve regurgitation for long-term event-free survival.  Therefore, subgroup analysis based on TR residual is relevant.

A CED study would be considered successful if it demonstrated all of the following:

  • Clinically meaningful improvement in health outcomes in Medicare beneficiaries following T-TEER for treatment of symptomatic TR, in comparison to OMT.
  • Satisfactory risk/benefit profile of T-TEER compared with tricuspid valve surgery in Medicare beneficiaries with symptomatic TR.
  • Specific patient and disease phenotype subgroups likely to benefit from T-TEER.
  • Treatment conditions (operator, procedure, and facility characteristics) that contribute to expected outcomes described above.

At the time of writing this decision memorandum, there are no published professional society guidelines for appropriate facility procedural volume requirements specific to T-TEER programs.  Further, there are minimal data on treatment conditions that support outcomes comparable to those in the published RCTs on T-TEER.  CED requirements included in this final decision seek to create the evidence basis for a future NCD that articulates the treatment conditions that promote best patient outcomes following T-TEER.

2.                Evidence Questions – Answered

Our initial literature search and review of the evidence on the clinical utility of T-TEER for Medicare beneficiaries with TR were guided by three general questions.  Answers to these questions inform the overarching question of whether T-TEER meets the reasonable and necessary standard under §1862(a)(1)(A) of the Act.

Q1: Is the evidence sufficient to conclude that T-TEER is reasonable and necessary for the treatment of Medicare beneficiaries with symptomatic TR?

No - The quality and strength of the evidence, discussed above and below, are insufficient to make this determination and T-TEER in this population is not reasonable and necessary under § 1862(a)(1)(A) of the Act because critical evidentiary gaps remain.

Benefits vs. Harms
The TRILUMINATE Pivotal trial did not show differences between groups in mortality, nor in the rate of HF hospitalization at one year.  In addition, performance on the primary outcome was driven by QoL measures.  In this context, it is impossible to assess true benefit against OMT alone, and treatment benefit for hospitalization, total hospitalizations, and survival have not been shown.  The investigators emphasized the importance of longitudinal study follow up for survival and hospitalizations (Sorajja et al., 2023).  Findings of the Tri.Fr study were similar to that of TRILUMINATE at one year, showing significant improvements for the T-TEER group for the primary composite endpoint (driven by NYHA class and PGA scores), with no significant difference for cardiovascular-related hospitalizations or mortality. It is noted that as of the date of this final decision memorandum, the FDA-approved label indicates that information provided to the patient should include that “Patients on average are unlikely to experience any survival benefit or a reduced rate of heart failure-related hospitalization.” While two year TRILUMINATE results showed an improvement in recurrent HF hospitalizations for the T-TEER group compared to OMT, mortality was not significantly impacted.

Because OMT was not standardized and because of the lack of analysis of disease subgroups, improvement in health outcomes following T-TEER is not yet thoroughly understood in comparison to OMT for TR.  It is notable that a percentage of patients in the medical arm improved, suggesting that there was benefit from optimizing medical therapy.  Given the trial design, the magnitude of benefit of the device over standardized OMT is unclear.

Q2: Is there evidence that specific characteristics or comorbidities make patients more or less likely to benefit from T-TEER?

Uncertain – Evidence is lacking.

As noted by the TRILUMINATE Pivotal investigators, patients in the pivotal trial were highly selected with few comorbidities.  A high percentage of enrolled patients were NYHA class II, and HF hospitalizations in the year preceding randomization were low.  Patients with HF with reduced ejection fraction, a major cause of secondary TR, were underrepresented in the trial.  It remains unknown whether a population with a higher-risk profile would derive a benefit from T-TEER over medical therapy alone.  Further, patients with a good QoL were not shown to benefit from T-TEER.  It is noted that the FDA label indicates that information provided to the patient should include that “Patients who have good baseline quality of life and functional status may not experience further improvement in these attributes following treatment with the TriClip G4 System.”

Subgroup Analysis
Patients in the trials had various underlying causes of TR, yet no subgroup analyses are available to support patient selection.  Due to small sample sizes, subgroup analysis based on TR etiology is not possible, limiting understanding of the benefit of the intervention for specific TR phenotypes.  In patients with LH failure, GDMT is well-defined.  Analysis of this specific subgroup, with adherence to GDMT documented in the trial, would help to clarify device benefit in this population.  More evidence is needed for patients with chronic kidney disease and patients with indwelling CIEDs.

Q3: Are specific treatment conditions necessary to achieve T-TEER outcomes similar to those demonstrated in the clinical studies reviewed in this analysis?

Uncertain – As noted by the trial investigators, degree of residual valve regurgitation has implications for long-term event-free survival. The RCTs were performed in specialized centers with selected procedural operators with experience in performance of percutaneous structural heart procedures. In addition, the study authors for the TRILUMINATE Pivotal Trial have indicated that high rates of attaining moderate-or-less TR were likely related to operator experience. No stratification nor subgroup analysis is available based on treatment conditions and there are no published studies or guidelines that address the impact of the qualifications of procedural operators on patient outcomes during and after T-TEER. However, as with many interventions, data on TAVR, surgical valve replacement, and transcatheter mitral valve repair suggest that facility and/or practitioner volumes may predict patient outcomes (Vemulapalli et al., 2019; Salemi et al., 2019; Awtry et al., 2024; Vassileva et al., 2015; Chhatriwalla et al., 2019).

There is little evidence to date that outcomes achieved in rigorous trials at highly selected sites can be replicated in the real world.  Treatment conditions that provide an appropriate balance of satisfactory health outcomes and optimal patient access are currently unknown for this technology.

Based on the totality of the evidence, CMS finds further justification that coverage under CED is appropriate.  We anticipate that CED with pre-specified analyses of the impact of operator and facility characteristics on outcomes, will help to guide future decisions relative to treatment conditions for T-TEER.

C.              Benefit Category

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 §1812 (Scope of Part A); §1832 (Scope of Part B); or §1861(s) (Definition of Medical and Other Health Services) of the Act.

T-TEER qualifies as:

  • Inpatient hospital services
  • Physicians’ services

Note: This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service.

D.              Shared Decision-Making

CMS recognizes the importance of shared decision-making (SDM) in many clinical scenarios and has required SDM in other NCDs (for example, implantable cardiac defibrillators: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=110 Opens in a new window).  CMS supports clinician-patient SDM for T-TEER for TR, but recognizes that there is no fully developed tool available at this time.  CMS strongly encourages standardized decision aids or tools.  The National Quality Forum (NQF) has published standards for decision aids (www.qualityforum.org/Projects/c-d/Decision_Aids/Final_Report.aspx Opens in a new window) to facilitate the decision-making process between a patient and physician and will be monitoring this space closely.

V.            History of Medicare Coverage

A.              Current National Coverage Request

This is CMS’ first NCA on T-TEER.  This request was externally initiated.  CMS received a complete, formal request to open an NCA on the topic of transcatheter edge-to-edge repair for tricuspid valve regurgitation from Abbott.  The request letter is available at https://www.cms.gov/files/document/id316.pdf Opens in a new window.  Abbott is participating in the Transitional Coverage for Emerging Technologies (TCET) pilot program and tested the processes and concepts of TCET.

B.              Timeline of NCA Milestones

Date Milestone

October 3, 2024

CMS posts a tracking sheet announcing the opening of the NCA.  The first 30-day public comment period begins.

November 2, 2024

First public comment period ends.  CMS receives 64 comments.

April 3, 2025

CMS posts proposed Decision Memorandum.  Second 30-day public comment period begins.

May 3, 2025

Second public comment period ends.  CMS receives 30 comments.

July 2, 2025

CMS posts final Decision Memorandum.

VI.          Appendices

Appendix A: Medicare National Coverage Determinations Manual Language

Draft

This draft NCD is subject to formal revisions and formatting changes prior to the release of the final NCD contractor instructions and publication in the Medicare National Coverage Determinations Manual.

Table of Contents
(Rev.)

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

A.   General

Transcatheter Edge-to-Edge Repair for Tricuspid Valve Regurgitation (T-TEER) is used in the treatment of tricuspid regurgitation.

B.   Nationally Covered Indications

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 below:

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 TR.

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 B.1; furnish items and services only through practitioners who meet the criteria in section 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 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. https://www.cms.gov/medicare-coverage-database/view/medicare-coverage-document.aspx?mcdid=38 Opens in a new window

    1. Sponsor/Investigator: The study is conducted by sponsors/investigators with the resources and skills to complete it successfully.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. Sensitivity Analyses: Sponsors/investigators will demonstrate robustness of results by conducting pre-specified sensitivity testing using alternative variable or model specifications as appropriate.
    14. 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).
    15. 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.
    16. 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.
    17. 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 Social Security 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.

    (This NCD last reviewed July 2025.)



    Appendix B: Referenced Materials

    Study Characteristics Intervention(s) and Patient Characteristics Outcomes
    Efficacy Safety
    TRILUMINATE Studies

    Reference: Tang et al., 2025

    Country: US, Europe, Canada

    Study Design: RCT, multi-center (68 centers in the US, Europe, and Canada)

    Purpose: To report outcomes from the full randomized cohort of the TRILUMINATE Pivotal trial. Additional enrollment may further support the safety and effectiveness of T-TEER through 1 year.

    Funding Source: Abbott

    Qualitya: No formal quality assessment was performed.

    Notes: NA

    Intervention: T-TEER with TriClip or TriClip G4m
    TriClip: 84/281 (29.9%)
    TriClip G4: 197/281 (70.1%)

    Comparator: MT alone

    Follow-up: baseline, 1, 6, and 12 months

    Patients (N): 572
    T-TEER: 285
    MT: 287

    Age, years, T-TEER vs. MT, mean (SD): 78.1 (7.9) vs. 78.1 (7.6)

    Age ≥ 65, n (%): NR

    Sex, female, T-TEER vs. MT, n (%): 168 (58.9) vs. 169 (58.9)

    Race, n (%): NR

    Diagnosis:
    TR severity, T-TEER vs. MT, n (%):
    Moderate: 6 (2.2) vs. 4 (1.5)
    Severe: 70 (25.1) vs. 78 (28.5)
    Massive: 67 (24.0) vs. 51 (18.6)
    Torrential: 136 (48.7) vs. 141 (51.5)
    KCCQ score, T-TEER vs. MT, n (%):
    Overall summary: 55.6 (22.9) vs. 54.6 (23.8)

    Comorbidities, T-TEER vs. MT, n (%):
    Body mass index, kg/m2: 26.8 (5.8) vs. 27.1 (5.5)
    Atrial fibrillation: 236 (82.8) vs. 266 (92.7)
    Hypertension: 231 (81.1) vs. 234 (81.5)
    Prior stroke: 18 (6.3) vs. 29 (10.1)
    Diabetes: 49 (17.2) vs. 45 (15.7)
    Peripheral vascular disease: 22 (7.7) vs. 27 (9.4)
    Prior CABG: 48 (16.8) vs. 51 (17.8)
    Prior mitral or aortic intervention: 108 (37.9) vs. 99 (34.5)
    COPD: 37 (13.0) vs. 45 (15.7)
    Permanent pacemaker or defibrillator: 47 (16.5) vs. 47 (16.4)

    Inclusion criteria: See Sorajja et al., 2023 below

    Exclusion criteria: See Sorajja et al., 2023 below

    Primary endpoint:
    Change in KCCQ-OS, baseline over the 1-year follow-up, T-TEER – MT, mean (95% CI):
    Overall summary: 13.5 points (9.5-17.5), p<0.001

    Improvement in KCCQ-OS from baseline to 1 year, T-TEER vs. MT:
    16.5 vs. 3.3
    Between group difference (95% CI): 13.2 (9.5, 16.9) (p<0.0001)

    Improvement of 15+ points in KCCQ-OS from baseline to 1 year, T-TEER vs. MT: 52.3% vs. 23.5% (p<0.0001)

    Reduction in TR from baseline to 30 days, T-TEER vs. MT:
    Moderate or less: 92.4% vs. 6.3% (p<0.0001)
    Mild or less: 53.3% vs. 1.0% (p<0.0001)

    Secondary endpoint:
    Freedom from MAEs through 30 days, T-TEER only, n (%):

    281 (98.9), p<0.001***

    Other safety outcomes:
    MAEs through 30 days, T-TEER only, n (%):

    CV mortality: 1 (0.4)
    MI: 0 (0)
    Stroke: 1 (0.4)
    New-onset renal failure: 2 (0.7)
    Non-elective cardiac surgery: 0 (0)

    Adjudicated MAEs through 1 year, T-TEER vs. MT, n (%):
    All-cause mortality: 24 (8.6) vs. 22 (8.0)
    CV mortality: 16 (5.8) vs. 11 (4.0)
    HF-related: 12 (4.4) vs. 8 (2.9)
    Non-HF-related: 4 (1.5) vs. 3 (1.1)
    HF hospitalization: 33 (12.0) vs. 36 (13.2)
    Stroke: 3 (1.1) vs. 3 (1.1)
    TV surgery: 5 (1.8) vs. 7 (2.5)
    Tricuspid intervention: 7 (2.6) vs. 4 (1.6)

    AEs through 30 days, T-TEER only, n (%):
    Major bleeding: 9 (3.2)
    SLDA: 16 (5.7)
    Device embolization: 0 (0)
    Device thrombosis: 0 (0)

    In-hospital death through 30 days, T-TEER only, n (%): 0 (0)

    HF Hospitalizations at 1 year, T-TEER vs. MT, annualized rate (95% CI): 0.17 vs. 0.20 (p=0.40)

    Reference: Kar et al., 2025

    Country: US, Europe, Canada

    Study Design: RCT, multi-center (68 centers in the US, Europe, and Canada)

    Purpose: To report 2 year outcomes from the TRILUMINATE Pivotal trial.

    Funding Source: Abbott

    Qualitya: No formal quality assessment was performed.

    Notes: NA

    Intervention: T-TEER with TriClip

    Comparator: MT alone

    Follow-up: 2 y

    Patients (N): 572
    T-TEER: 285
    MT: 287

    Age, years, T-TEER vs. MT, mean (SD): 78.1 (7.9) vs. 78.1 (7.6)

    Age ≥ 65, n (%): NR

    Sex, female, T-TEER vs. MT, n (%): 168 (58.9) vs. 169 (58.9)

    Race, n (%): NR

    Diagnosis:
    TR severity, T-TEER vs. MT, n (%):
    Moderate: 6 (2.2) vs. 4 (1.5)
    Severe: 70 (25.1) vs. 78 (28.5)
    Massive: 67 (24.0) vs. 51 (18.6)
    Torrential: 136 (48.7) vs. 141 (51.5)
    KCCQ score, T-TEER vs. MT, n (%):
    Overall summary: 55.6 (22.9) vs. 54.6 (23.8)

    Comorbidities, T-TEER vs. MT, n (%):
    Body mass index, kg/m2: 26.8 (5.8) vs. 27.1 (5.5)
    Atrial fibrillation: 236 (82.8) vs. 266 (92.7)
    Hypertension: 231 (81.1) vs. 234 (81.5)
    Prior stroke: 18 (6.3) vs. 29 (10.1)
    Diabetes: 49 (17.2) vs. 45 (15.7)
    Peripheral vascular disease: 22 (7.7) vs. 27 (9.4)
    Prior CABG: 48 (16.8) vs. 51 (17.8)
    Prior mitral or aortic intervention: 108 (37.9) vs. 99 (34.5)
    COPD: 37 (13.0) vs. 45 (15.7)
    Permanent pacemaker or defibrillator: 47 (16.5) vs. 47 (16.4)

    Inclusion criteria: See Sorajja et al., 2023 below

    Exclusion criteria: See Sorajja et al., 2023 below

    Annualized rate of recurrent HFH through 2 years:
    Device: 0.19 [95% CI: 0.15, 0.23]
    Control: 0.26 [95% CI: 0.22, 0.31]
    Notes: Events/patient-year, p=0.02)

    Freedom from tricuspid valve intervention (2 years):
    Device: 96.2 %
    Control: 38.5%

    Freedom from all-cause mortality (2 years):
    Device: 82.1%
    Control: 82.9%

    Freedom from tricuspid valve surgery (2 years):
    Device: 97.7%
    Control: 95.7%

    KCCQ improvement (2 years), mean (SD):
    Device: 15.4 (23.4)
    Notes: KCCQ improvements in the device group were not significantly different from 30 days, 1 year, and 2 years.

    Adverse events (2 years), %:
    Stroke: 1.9
    TIA: 1.7
    Tricuspid valve surgery: 2.3
    Cardiogenic shock: .4
    Notes: Numbers above are for the device group. These AEs were infrequent and comparable to rates in the control group.

    Reference:Arnold et al., 2024

    Country:US, Europe, Canada

    Study Design: RCT, multi-center (80 centers in the US, Europe, and Canada)

    Purpose: To better understand the health status benefits of T-TEER within the TRILUMINATE Pivotal trial.

    Funding Source: Abbott Medical Devices; study conducted by Abbott under the direction of academic authors

    Qualityα: Adequate randomization.  Double-blinding not possible; however, AEs adjudicated by independent committee, and QoL assessment done by blinded personnel with standardized script.  Echo assessors unblinded.  BL characteristics similar between groups.  ITT analysis used.  Data for the primary endpoint, change from BL to 1 year in the KCCQ-Overall Summary score, was available for 147/175 patients in T-TEER arm and 149/175 patients in the MT group; <10% difference in attrition between groups.

    Notes: NA

    Intervention: T-TEER with Tri-Clip

    Comparator: MT alone

    Follow-up: baseline, 1, 6, and 12 months

    Patients (N): 350
    T-TEER: 175
    MT: 175

    Age, years, T-TEER vs. MT, mean (SD): 78.0 (7.4) vs. 77.6 (7.4)

    Age ≥ 65, n (%): NR

    Sex, female, T-TEER vs. MT, n (%): 96 (56.8) vs. 86 (52.8)

    Race, n (%): NR

    Diagnosis:
    TR severity, T-TEER vs. MT, n (%):
    Moderate: 4 (2.4) vs. 2 (1.3)
    Severe: 44 (26.2) vs. 47 (30.3)
    Massive: 36 (21.6) vs. 25 (16.2)
    Torrential: 83 (49.4) vs. 80 (51.6)
    KCCQ score, T-TEER vs. MT, n (%):
    Overall summary: 56.4 (23.5) vs. 55.2 (23.8)
    Physical limitations: 59.1 (24.4) vs. 60.4 (25.6)
    Total symptoms: 63.0 (24.8) vs. 59.6 (25.8)
    Self-efficacy: 79.5 (22.0) vs. 80.5 (22.1)
    Quality of life: 50.0 (26.4) vs. 46.4 (26.1)
    Social limitation: 52.4 (31.5) vs. 54.6 (30.8)

    Comorbidities, T-TEER vs. MT, n (%):
    Body mass index, kg/m2: 27.0 (5.8) vs. 26.9 (5.4)
    Atrial fibrillation: 148 (87.6) vs. 151 (92.6)
    Hypertension: 138 (81.7) vs. 131 (80.4)
    Prior stroke: 11 (6.5) vs. 16 (9.8)
    Diabetes: 27 (16.0) vs. 26 (16.0)
    Peripheral vascular disease: 16 (9.5) vs. 15 (9.2)
    Prior CABG: 31 (18.3) vs. 32 (19.6)
    Prior mitral or aortic intervention: 66 (39.1) vs. 55 (33.7)
    Chronic lung disease: 17 (10.1) vs. 23 (14.1)
    Permanent pacemaker or defibrillator: 27 (16.0) vs. 20 (12.3)

    Inclusion criteria: See Sorajja et al., 2023 below

    Exclusion criteria: See Sorajja et al., 2023 below

    Primary endpoint:
    Change in KCCQ-OS, baseline over the 1-year follow-up, T-TEER – MT, mean (95% CI):
    Overall summary: 10.4 points (6.3-14.6), p<0.001
    Physical limitations: 7.3 (2.6 to 12.0), p=0.003
    Total symptoms: 6.8 (2.3 to 11.4), p=0.004
    Quality of life: 14.1 (9.1 to 19.2), p<0.001
    Social limitation: 14.0 (7.8 to 20.3), p<0.001
    Physical component summary: 5.2 (3.3 to 7.1), p<0.001
    Mental component summary: 1.5 (-0.9 to 3.8), p=0.216
    Other endpoints:
    Alive with moderate improvement (KCCQ-OS change 10+ points), T-TEER-MT, absolute risk difference (95% CI):
    1 month: 25.4 (14.9-35.8), p<0.001
    6 months: 23.4 (12.4-34.4), p<0.001
    1 year: 19.3 (8.1-30.5), p=0.001

    Alive with large improvement
    (KCCQ-OS change 20+ points), T-TEER-MT, absolute risk difference (95% CI):
    1 month: 18.6 (9.5-27.8), p<0.001
    6 months: 16.2 (5.5-26.9), p=0.003
    1 year: 26.0 (16.1-35.8), p<0.001

    Alive and well (KCCQ-OS change 60+ points and decline < 10), T-TEER-MT, absolute risk difference (95% CI):
    1 month: 19.3 (8.7-29.9), p<0.001
    6 months: 26.5 (16.0-36.9), p<0.001
    1 year: 28.9 (18.2-39.5), p<0.001

    Change in TR from baseline (per 1-grade decrease): 4.1 (1.8 to 6.5), p=0.001
    Adjusted for the following:
    Baseline KCCQ-OS Score (per 10 points): -5.1 (-6.0 to -4.1), p<0.001

    Age (per 10 y): -3.1 (-5.8 to -0.4), p=0.025
    Male: -2.3 (-6.6 to -2.1), p=0.306
    Chronic lung disease: 4.8 (-1.0 to 10.5), p=0.103
    Baseline TR grade (REF: moderate):
    Severe: 11.4 (-4.8 to 27.5), p=0.168
    Massive: 4.6 (-12.2 to 21.5), p=0.589
    Torrential: 2.8 (-14.5 to 20.1), p=0.752

    Estimated effect of T-TEER on KCCQ-OS at 1 year, mean difference (95% CI):
    Age, < 78 years vs. ≥ 78 years:
    14.6 (7.9 to 21.4) vs. 6.5 (0.1 to 12.9), p=0.088
    Sex, female vs. male:
    9.7 (3.6 to 15.8) vs. 10.7 (3.6 to 17.8), p=0.835
    Previous aortic or mitral intervention, no vs. yes:
    11.6 (5.7 to 17.4) vs. 8.5 (0.7 to 16.3), p=0.536
    Right ventricular end-diastolic diameter at base, <5 cm vs. ≥5 cm: 11.3 (4.4 to 18.2) vs. 9.8 (3.5 to 16.2), p=0.762
    Tricuspid annular plane systolic excursion, <1.7 cm vs. ≥1.7 cm: 13.8 (7.3 to 20.2) vs. 7.2 (0.2 to 14.1), p=0.174
    Central venous pressure, <10 mm Hg vs. ≥10 mm Hg: 14.3 (4.5 to 24.1) vs. 10.6 (2.5 to 18.6), p=0.565
    mPAP, <25 mm Hg vs. ≥25 mm Hg: 10.3 (3.4 to 17.1) vs. 10.8 (4.4 to 17.2), p=0.915
    Cardiac index, <2 L/min/m2 vs. ≥2 L/min/m2: 1.6 (-8.1 to 11.4) vs. 13.3 (8.0 to 18.6), p=0.041
    Severity of tricuspid regurgitation (baseline):
    Moderate: 2.4 (32.1 to 36.9),
    Severe: 12.7 (4.1 to 21.4),
    Massive: 9.9 (0.8 to 20.6),
    Torrential: 11.2 (4.5 to 18.0), p=0.617
    6-minute walk distance, <236 m vs. ≥ 236 m:
    5.6 (1.7 to 12.9) vs. 14.0 (7.9 to 20.1), p=0.086

    Change in KCCQ-Overall Summary at 1 month after T-TEER, HR (95% CI):
    Death: 0.76 (0.64-0.90)
    Heart failure hospitalization: 0.75 (0.64-0.89)
    Death or heart failure hospitalization: 0.74 (0.65-0.84)

    Note: HR is for a 10-point increase in KCCQ-Overall Summary.

    NR

    Reference: von Bardeleben et al., 2023 (TRILUMINATE Single-Arm, 2-year)

    Country: US, Europe

    Study Design: Multi-center (21 sites), prospective, single-arm, interventional study

    Purpose: To study the 2-year outcomes with the TriClip TEER system in symptomatic patients with moderate or greater TR

    Funding Source: Abbott

    Qualityα: NA
    No formal quality assessment performed due to single-arm study design.

    Notes: All MAEs adjudicated by independent committee.  Analyzable echo data available for 48/85 patients at 2 year (n=14 death, n=6 withdrawal, n=3 missed visit, n=14 lack of readable data)

    Intervention: T-TEER with TriClip

    Comparator: NA

    Length of follow-up, mean: 2 years

    Patients (N): 85

    Age, years, mean (SD): 77.8 (7.9)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 56 (66)

    Race, n (%): NR

    Diagnosis:
    TR etiology:
    Functional: 84%
    Degenerative: 12%
    Mixed: 4%
    NYHA Functional Class III/IV: 75%
    TR severity:
    Moderate or more severe: 100%

    Comorbidities:
    Atrial fibrillation: 92%
    Atrial hypertension: 86%
    Renal disease: 46%
    Diabetes: 22%
    Prior MI: 18%
    Prior mitral intervention: 33%
    CRT/ICD/PPM: 14%

    Inclusion criteria: See Nickenig et al., 2019 below

    Exclusion criteria: See Nickenig et al., 2019 below

    Note: Independent eligibility committee comprised of interventional cardiologists, CV surgeons, HF specialists, and echocardiographers evaluated each subject for enrollment.

    Reduction to TR severity ≤ moderate, %:
    Overall, 2-years vs. BL: 60% vs. 4%, p<0.0001***, favoring 2 year
    Torrential/Massive, at 2 year: 2%

    2-years vs. 30-days: 60% vs. 63%, p=0.90
    Note: TR reduction of at least 1 grade was achieved in 85.4% (41/48) of subjects at 2 years.  The reduction in TR achieved at 30 days was maintained through 2 years for 75% (36/48) of subjects.  No change between 30-day and 2-year TR severity was observed in 50% (24/48) of subjects, while a further reduction was seen in 25% (12/48) of subjects.

    Functional status, NYHA Class I or II, %:
    2 year vs. BL: 81% vs. 33%, p<0.0001***, favoring 2 years
    2 year vs. 30 days: 81% vs. 85%, p=0.59

    Functional status, 6MWT, mean (SD) meters:
    2 year vs. BL: 324 (NR) vs. 263 (NR)
    Difference: 60 (SD: 23), p<0.01**, favoring 2 year

    HF symptoms, KCCQ score, mean (SD) points:
    2 year vs. BL: 66.3 (NR) vs. 53.3 (NR)
    Difference: 13 (NR), p<0.0001***, favoring 2 year

    TR reduction of ≥1 grade, at 2 year, n/N (%): 41/48 (85.4)

    Right heart remodeling and RV function, BL vs. 2 year, mean (SD):
    RVEDD, cm: 5.24 (0.65) vs. 4.70 (0.69), p=0.0003***, favoring 2 year but no significant change from 1 year
    Tricuspid annular diameter S-L, cm: 4.28(0.53) vs. 4.32 (0.62), p=0.6833
    Right atrial volume, mL: 121.24 (48.29) vs. 125.45 (58.36), p=0.7165
    RV FAC, %: 38.95 (6.08) vs. 38.29 (3.59), p=0.6111
    RV systolic pressure, mmHg: 39.69 (7.49) vs. 37.56 (12.04), p=0.5294
    TAPSE, cm: 1.48 (0.3) vs. 1.68 (0.47) m, p=0.0155***, favoring 2 year
    RV global longitudinal strain, %: -15.10 (3.07) vs. -14.00 (3.62), p=0.3639

    Note: Most of the remodeling occurred within the first 30 days post-procedure.  However, TAPSE and RVEDD showed signals of continued favorable remodeling through 2 years

    Diuretic usage, BL to 2 year, n (%):
    Same: 51/56 (91.1)
    Decreased: 4/56 (7.1)
    Increased: 1/56 (1.8)

    MAE, at 2 year, n/N (%): 15/84 (17.9)
    CV mortality: 11/84 (13.1)
    MI: 1/84 (1.2)
    Stroke: 2/84 (2.4)
    New onset renal failure: 3/84 (3.6)
    Endocarditis requiring surgery: 0 (0)
    Nonelective CV surgery for device-related AE: 0 (0)

    Other safety endpoints, at 2 years, n/N (%):
    All-cause mortality: 14/84 (18.7)
    Major bleeding: 10/84 (11.9)
    Pulmonary thromboembolism: 0/84 (0)
    New onset liver failure: 1/84 (1.2)
    New onset atrial fibrillation: 2/84 (2.4)
    SLDA: 5/84 (6)
    Embolization: 0/48 (0)
    Mean tricuspid gradient ≥5mmHg: 2/44 (4.5)

    All-cause hospitalization, 1 year pre- vs. 2 year post-TriClip repair, events per P-Y:
    1.30 vs. 0.66
    Difference: 49%, p<0.0001**, favoring 2 year post-TriClip repair
    Note: Analysis based on N=56.
    Driven by 84% reduction in HF hospitalization rate 1 year pre- vs. 1 year post-TriClip repair, events per P-Y: 0.50 vs 0.08, p<0.0001

    Mortality/HF hospitalization, at 2 years, TR ≤moderate vs. 30-day TR ≥severe: HR: 0.40 (95% CI: 0.16-0.96), p=0.034*, favoring a lower mortality/HF hospitalization rate for patients with a reduction to ≤moderate TR at 30 days post-procedure

    Reference: Sorajja et al., 2023 (TRILUMINATE Pivotal)

    Country: US, Canada, Europe

    Study Design: Multi-center (65 sites), prospective, open-label, RCT

    Purpose: To evaluate the safety and efficacy of T-TEER in symptomatic patients with severe TR

    Funding Source: Abbott

    Qualityα: Good
    Adequate randomization.  Double-blinding not possible; however, AEs adjudicated by independent committee, and QoL assessment done by blinded personnel with standardized script.  Echo assessors unblinded.  BL characteristics were similar between groups.  ITT analysis was used for all endpoints except freedom from MAEs. 152/175 patients in TEER arm completed 12-mo visit (7 withdrew, 16 died). 150/175 patients in MT arm completed 12-mo visit (2 missed the visit, 9 withdrew, 14 died). 86% completion rate overall; <10% difference in attrition between groups.

    Notes: N=350 provided 84% power to show superiority of TEER vs. MT in the primary analysis, with two-sided α=0.05.

    Intervention: T-TEER with TriClip or TriClip G4
    TriClip: 81 (47.1%)
    TriClip G4: 91 (52.9%)

    Comparator: MT alone

    Length of follow-up, mean: NR
    n=152 and n=150 patients completed 12-mo visit, n=155 and n=155 completed 6-mo visit, and n=168 and n=162 completed 30-day visit in TEER and MT groups, respectively.

    Patients (N): 350
    TEER: 175
    MT: 175

    Note: 172 patients had device implant attempted, and 170 patients had devices actually implanted.

    Age, years, mean (SD, range): 78 (7, 51-96)
    TEER: 78.0 (7.4)
    MT: 77.8 (7.2)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 192 (54.9)
    TEER: 98 (56.0)
    MT: 94 (53.7)

    Race, n (%): NR

    Diagnosis:
    NYHA Class III or IV, n (%):
    TEER: 104 (59.4) vs. MT: 97 (55.4)
    Functional TR, n (%):
    TEER: 165 (94.8) vs. MT: 158 (92.9)
    Severity of TR, TEER vs. MT, n (%):
    Moderate: 4 (2.3) vs. 2 (1.2)
    Severe: 44 (25.4) vs. 49 (29.7)
    Massive: 37 (21.4) vs. 30 (18.2)
    Torrential: 88 (50.9) vs. 84 (50.9)
    KCCQ score, mean (SD): TEER: 56.0 (23.4) vs. MT: 54.1 (24.2)

    Comorbidities, TEER vs. MT, n (%):
    Atrial fibrillation:153 (87.4) vs. 162 (92.6)
    Atrial flutter: 20/174 (11.4) vs. 22/174 (12.6)
    Dyslipidemia: 117 (66.9) vs. 92 (52.6)
    Hypertension: 142 (81.1) vs. 141 (80.6)
    Stroke: 11 (6.3) vs. 19 (10.9)
    TIA: 13 (7.4) vs. 17 (9.7)
    Diabetes: 28 (16.0) vs. 27 (15.4)
    Peripheral vascular disease: 16 (9.1) vs. 18 (10.3)
    Coronary artery bypass grafting: 31 (17.7) vs. 36 (20.6)
    PCI: 26 (14.9) vs. 23 (13.1)
    Kidney disease: 62 (35.4) vs. 62 (35.4)
    Liver disease: 11 (6.3) vs. 16 (9.1)
    COPD: 19 (10.9) vs. 24 (13.7)
    CRT, CRT-D, ICD, or PPM: 28 (16.0) vs. 24 (13.7)
    Previous cardiac or transcatheter therapy:
    Aortic-valve intervention: 27 (15.4) vs. 27 (15.4)
    Surgical mitral-valve repair: 14 (8.0) vs. 9 (5.1)
    Percutaneous mitral-valve repair: 18 (10.3) vs. 22 (12.6)
    Mitral-valve replacement: 10 (5.7) vs. 9 (5.1)
    TV repair: 1 (0.6) vs. 0 (0)

    Inclusion criteria: Age ≥18 years; TR confirmed by an independent echocardiography laboratory as severe; symptomatic (NYHA functional class II, III, or IVa); sPAP <70mmHg; receiving stable (≥30 days) guideline-directed therapy for HF (includes medical and/or device therapy); no other CV conditions in need of interventional or surgical correction (e.g., severe aortic stenosis or mitral regurgitation); at intermediate or greater surgical risk as determined by the local heart team (board-certified specialists in cardiac surgery, interventional cardiology, echocardiology, and HF)

    Exclusion criteria: sPAP>70 mmHg or fixed pre-capillary pulmonary hypertension; severe uncontrolled hypertension (SBP≥180mmHg and/or DBP≥110mm Hg); any prior TV procedure that would interfere with placement of TriClip; indication for left-sided or pulmonary valve correction in prior 60 days; pacemaker or ICD leads that would prevent appropriate placement of the TriClip clip; TV stenosis; LVEF≤20%; TV leaflet anatomy which may preclude clip implantation, proper clip positioning on the leaflets, or sufficient reduction in TR (includes calcification in the grasping area, severe coaptation defect (>2cm) of the tricuspid leaflets, severe leaflet defect(s), Ebstein Anomaly); TV anatomy not evaluable by TTE and TEE; active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease; MI or known unstable angina within prior 30 days; PCI within prior 30 days; hemodynamic instability (SBP<90 mmHg with or without afterload reduction, cardiogenic shock or the need for inotropic support, intra-aortic balloon pump, or other hemodynamic support device); CVA within prior 90 days; chronic dialysis, bleeding disorders or hypercoagulable state, active peptic ulcer or active GI bleeding; evidence of intracardiac, inferior vena cava, femoral venous mass, thrombus, or vegetation; life expectancy <12 months

    Note: Patients judged to have a high likelihood of achieving moderate or less residual TR after TEER by an independent eligibility committee were placed into the randomized trial arm.  Patients who were deemed likely to achieve at least a one grade reduction but not achieve moderate or less residual TR were assigned to the single-arm cohort.  Patients who were unlikely to have any reduction in TR were excluded.

    Primary composite endpoint:
    All-cause mortality or TV surgery, HF hospitalization, and improvement in QoL measured by KCCQ), at 1 year, TEER vs. MT:
    WR: 1.48 (95% CI: 1.06 to 2.13), p=0.02*, favoring TEER
    Note: Assessed in first 350 patients to complete 12-month follow-up.

    Sensitivity analyses of primary endpoint, at 1 year, TEER vs. MT, WR (95% CI):
    As treated: 1.59 (1.13 to 2.31), favoring TEER
    Per-protocol (randomized patients without major PDs): 1.44 (1.00 to 2.11)
    COVID-19 inclusion (events after COVID diagnosis): 1.43 (1.02 to 2.04), favoring TEER

    Components of composite endpoint, at 1 year, TEER vs. MT:
    All-cause mortality or TV surgery, n (%):
    16 (9.4) vs. 18 (10.6), p=0.75
    HF hospitalization, n events per P-Y:
    0.21 vs. 0.17, p=0.41
    Met improvement in QoL definition, n (%):
    73 (49.7) vs. 39 (26.4), p<0.0001***, favoring TEER

    Secondary endpoints:
    QoL, increase in KCCQ from BL to 1-year, mean points (SD):
    With imputation (score of 0 for patients with HF-related death from CV causes or had TV surgery before 1-year), TEER vs. MT:
    12.3 (1.8) vs. 0.6 (1.8)
    Difference: 11.7 (95% CI: 6.8 to 16.6), p<0.001***, favoring TEER
    Without imputation, TEER vs. MT: 15.2 (22.3) vs. 4.8 (18.3), p<0.001***, favoring TEER
    Multiple imputation for missing data, TEER vs. MT: 16.0 (1.5) vs. 5.1 (1.4)
    Difference: 10.9 (6.9 to 14.8), p<0.001***, favoring TEER
    Sensitivity analysis (competing risk of death), difference in point change, TEER vs. MT:
    9.9 (95% CI: 6.6 to 13.3), p<0.001***, favoring TTER
    Among ≤moderate vs. ≥severe residual TR, at 1 year:
    15.6 (22.0) vs. 3.8 (18.4)
    Among worsened vs. no change vs. 1 grade vs. ≥2 grade reduction in TR, at 1 year:
    0 (0) vs. 2 (NR) vs. 6 (NR) vs. 18 (NR)

    Reduction to ≤ moderate TR severity, TEER vs. MT, n (%):
    At 30 days: 140 (87) vs. 7 (4.8), p<0.001***, favoring TEER
    Sensitivity analysis (multiple imputation for missing data), at 30 days: 151 (86.3) vs. 13 (7.2), p<0.001***, favoring TEER
    At 1 year: NR (88.1) vs. NR (5.7)

    Change in 6MWT from BL to 1 year, TEER vs. MT, mean (SD) meters:
    -8.1 (10.5) vs. -25.2 (10.3)
    Difference: 17.1 (95% CI: -12.0 to 46.1), p=0.25
    Without imputation: 11.5 (111.4) vs. -8.7 (109.7)
    Sensitivity analysis (multiple imputation for missing data): 9.8 (9.2) vs. 1.5 (9.2)
    Difference: 8.3 (95% CI: -17.0 to 33.7), p=0.52
    Sensitivity analysis (competing risk of death), difference in distance: 1.2 (-4.8 to 7.0), p=0.69

    Note: Improvement in QoL defined as increase of ≥15 points in KCCQ score (range 0-100), with higher scores = better QoL).
    The Severity of TR was assigned a grade of 1 (trace or mild), 2 (moderate), 3 (severe), 4 (massive), or 5 (torrential).
    WR calculated by forming all possible pairs of one patient from the TEER group and one patient from the control group, then dividing the # of pairs in which the patient in the TEER group has a better outcome (i.e., a win in the TEER group) by the # of pairs in which a patient in the control group has a better outcome (i.e., a win in the control group).

    Other endpoints:
    NYHA Class I or II at 1 year, TEER vs. MT, n (%):
    125/149 (83.9) vs. 88/148 (59.5)
    Note: Paired analysis shows 45.6% and 46.6% of TEER and MT patients, respectively, in NYHA Class I or II at Baseline.

    Procedural outcomes, TEER only, n (%):
    Technical success: 170 (98.8)
    Device success: 144 (88.9)
    Procedural success: 141 (87.0)

    Note: Technical success = alive with successful access, delivery and retrieval of the device delivery system, deployment and correct positioning of a TriClip, no need for additional unplanned or emergency surgery or reintervention related to the device or access procedure.
    Device success = alive with original intended Clip(s) in place, no additional surgical or interventional procedures related to access or device since completion of the original procedure, intended performance of the Clip(s) (≥1 grade improvement in TR severity, no embolization, SLDA, absence of para-device complications).
    Procedural success = device success, no device or procedure related serious adverse event.

    Diuretic usage, BL to 1 year, TEER vs. MT, n/N (%):
    Decrease >50% or stop: 7/159 (4.4) vs. 9/169 (5.3)
    Stable: 136/159 (85.5) vs. 141/169 (83.4)
    Increase >100% or new usage: 12/159 (7.5) vs. 18/169 (10.7)

    Secondary endpoint:
    Freedom from MAEs through 30 days, TEER only, n (%):
    169 (98.3), p<0.001***

    Other safety outcomes:
    MAEs through 30 days, TEER only, n (%):
    CV mortality: 1 (0.6)
    MI: 0 (0)
    Stroke: 0 (0)
    New-onset renal failure: 2 (1.2)
    Non-elective cardiac surgery: 0 (0)

    Note: Death adjudicated as unrelated to device or procedure.

    Adjudicated MAEs through 1 year, TEER vs. MT, n (%):
    All-cause mortality: 15 (8.8) vs. 13 (7.7)
    CV mortality: 11 (6.5) vs. 8 (4.7)
    HF-related: 7 (4.1) vs. 5 (3.0)
    Non-HF-related: 4 (2.4) vs. 3 (1.8)
    HF hospitalization: 25 (14.9) vs. 20 (12.1)
    Stroke: 3 (1.8) vs. 2 (1.3)
    MI: 0 (0) vs. 0 (0)
    New-onset renal failure: 4 (2.3) vs. 1 (0.6)
    TV surgery: 3 (1.8) vs. 6 (3.6)
    Non-elective cardiac surgery for device AE:
    0 (0) vs. 0 (0)
    Tricuspid intervention: 4 (2.3) vs. 3 (2.0)
    Endocarditis requiring surgery: 0 (0) vs. 0 (0)

    AEs through 30 days, TEER only, n (%):
    Major bleeding: 8 (4.7)
    SLDA: 12 (7.0)
    Tricuspid mean gradient ≥5mmHg: 8 (5)
    Device embolization: 0 (0)
    Device thrombosis: 0 (0)

    AEs through 1 year, TEER vs. MT, n (%):
    Major bleeding: 9 (5.2) vs. 2 (1.1)
    Cardiogenic shock: 0 (0) vs. 1 (0.6)
    SLDA: 0 (0) vs. NA
    PPM or ICD placement: 5 (2.9) vs. 5 (2.9)

    In-hospital death, TEER only, n (%): 0 (0)

    HF Hospitalizations at 1 year, TEER vs. MT, annualized rate (95% CI):
    0.21 (0.15 to 0.30) vs. 0.17 (0.12 to 0.25)

    Reference: Lurz et al., 2021 (TRILUMINATE Single-Arm, 1-year)

    Country: US, Europe

    Study Design: Prospective, multi-center (21 sites), single-arm, interventional study

    Purpose: To study the 1-year outcomes with the TriClip TEER system in symptomatic patients with moderate or greater TR, including repair durability, clinical benefit, and safety

    Funding Source: Abbott

    Qualityα: NA
    No formal quality assessment was performed due to single-arm study design.

    Notes: All MAEs adjudicated by independent committee.  Analyzable echo data available for 62/85 patients at 1 year (n=7 death, n=5 withdrawal, n=4 missed visit, n=6 lack of readable data, n=1 unevaluable BL imaging); no significant differences between patients with vs. without 1-year echo follow-up.

    Intervention: T-TEER with TriClip

    Comparator: NA

    Length of follow-up, mean: 12 months

    Patients (N): 85

    Age, years, mean (SD): 77.8 (7.9)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 56 (66)

    Race, n (%): NR

    Diagnosis:
    TR etiology:
    Functional: 84%
    Degenerative: 12%
    Mixed: 4%
    NYHA Functional Class III/IV: 75%
    TR severity:
    Moderate or greater: 100%

    Comorbidities:
    Atrial fibrillation: 92%
    Atrial hypertension: 86%
    Renal disease: 46%
    Diabetes: 22%
    Prior MI: 17.6%
    Prior aortic intervention: 11%
    Prior mitral intervention: 33%
    Replacement - surgery: 25%
    Replacement - percutaneous: 7.1%
    Repair - surgery: 28.6%
    Repair - percutaneous: 32.1%
    Other: 14.3%
    CRT/ICD/PPM: 14%

    Inclusion criteria: See Nickenig et al., 2019 below

    Exclusion criteria: See Nickenig et al., 2019 below

    Note: Independent eligibility committee comprised of interventional cardiologists, CV surgeons, HF specialists, and echocardiographers evaluated each subject for enrollment.

    Reduction to TR severity ≤ moderate, n/N (%):
    Overall, 1-year vs. BL: 44/62 (71) vs. 5/62 (8), p<0.0001***, favoring 1 year
    BL Torrential/Massive, at 1 year: 22/62 (56)

    1-year vs. 30-days: 44/63 (70) vs. 38/63 (60), p=0.96
    Note: Between 30 days and 1 year, 21% (n=13/62) of patients had a further reduction in severity, 44% (n=27/62) had no change, and 21% (n=13/62) had a 1-grade increase.  Out of the 13 patients who had a 1-grade increase, 9 remained at moderate or less TR severity.

    Multivariate analysis of correlation between BL TR severity and ≤moderate TR severity at 1 year:
    Torrential: OR: 10.45, p=0.0007***, favoring severe BL TR
    Massive: OR: 4.34, p=0.03*, favoring severe TR

    Functional status, NYHA Class I or II, n/N (%):
    1 year vs. BL: 54/65 (83) vs. 20/65 (31), p<0.0001***, favoring 1 year
    1 year vs. 30 days: 55/66 (83) vs. 54/66 (82), p=0.39

    Functional status, 6MWT, mean (SD) meters:
    1 year vs. BL: 303.2 (15.6) vs. 272.3 (15.6)
    Difference: 31 (SD: 10.2, 95% CI: 11 to 51), p=0.0023**, favoring 1 year
    1 year vs. 6 months: 303.2 (15.6) vs. 312 (NR)
    Difference: -9 (95% CI: -25 to 7), p=0.2667

    HF symptoms, KCCQ score, mean (SD) points:
    1 year vs. BL: 72 (NR) vs. 52 (NR)
    Difference: 20 (SD: 2.61, 95% CI: 15 to 25), p<0.0001***, favoring 1 year
    1 year vs. 6 months: 72 (NR) vs. 66 (NR)
    Difference: 6 (SD: 2.7, 95% CI: 1 to 11), p=0.029*
    Note: Analysis based on N=66.

    TR reduction of ≥1 grade, at 1 year, n/N (%):
    Overall: 54/62 (87)
    BL Torrential/Massive: 35/39 (90)

    Right heart remodeling and RV function, BL vs. 1 year, mean (SD):
    RVEDD, cm: 5.28 (0.07) vs. 4.79 (0.08), p<0.0001***, favoring 1 year
    Tricuspid annular diameter S-L, cm: 4.34 (0.06) vs. 4.03 (0.07), p<0.0001***, favoring 1 year
    Right atrial volume, mL: 129 (5.84) vs. 116 (6.55), p=0.0166*, favoring 1 year
    RV FAC, %: 36.00 (0.85) vs. 38.19 (0.57), p=0.0057**, favoring 1 year
    RV systolic pressure, mmHg: 42.7 (1.08) vs. 43.9 (2.30), p=0.5727
    TAPSE, cm: 1.44 (0.03) vs. 1.59 (0.04) m, p=0.0002***, favoring 1 year
    RV global longitudinal strain, %: -14.1 (0.64) vs. -14.6 (0.86), p=0.5897

    Note: Most of the remodeling occurred within the first 30 days post-procedure.  However, TAPSE and RVEDD showed continued reverse modeling from 30 days through 1 year, with the majority of improvement occurring between 30 days and 1 year for TAPSE.

    Diuretic usage, BL to 1 year, n (%):
    Same (no more than 100% increase or 50% decrease in dose and maintained for ≥30 days): 66 (77.6)
    Decreased: 13 (15.3)
    Increased: 7 (8.2)

    MAE, at 1 year, n/N (%): 6/84 (7.1)
    CV mortality: 4/84 (4.8)
    MI: 1/84 (1.2)
    Stroke: 1/84 (1.2)
    New onset renal failure: 1/84 (1.2)
    Endocarditis requiring surgery: 0 (0)
    Nonelective CV surgery for device-related AE:
    0 (0)

    Other safety endpoints, at 1 year, n/N (%):
    All-cause mortality: 6/84 (7.1)
    Major bleeding: 10/84 (11.9)
    Pulmonary thromboembolism: 0/84 (0)
    New onset liver failure: 0/84 (0)
    New onset atrial fibrillation: 1/84 (1.2)
    SLDA: 5/65 (7.7)
    Embolization: 0/65 (0)
    Mean tricuspid gradient ≥5mmHg: 4/64 (6.3)

    HF hospitalization, 1 year pre- vs. 1-year post-TriClip repair, events per P-Y:
    1.30 vs. 0.78
    Difference: 40%, p=0.003**, favoring 1-year post-TriClip repair
    Note: Analysis based on N=70.

    Mortality/HF hospitalization, at 1 year, 30-day TR ≤moderate vs. 30-day TR ≥severe:
    8.8% vs. 24.5%
    HR: 0.31, p=0.041*, favoring a lower mortality/HF hospitalization rate for patients with a reduction to ≤moderate TR at 30 days post-procedure
    Note: Analysis based on N=70 (all patients with a 1-year follow-up).

    Reference: Nickenig et al., 2019 (TRILUMINATE Single-Arm, 6 months)

    Country: US, Europe

    Study Design: Prospective, multi-center (21 sites), single-arm, interventional study

    Purpose: To evaluate the safety and effectiveness of TriClip for reducing TR

    Funding Source: Abbott

    Qualityα: NA
    No formal quality assessment was performed due to single-arm study design.

    Notes: Primary safety analysis population was enrolled patients who had an attempted procedure (n=84).  Patients who did not reach 6-mo follow-up and did not have an MAE during previous follow-ups were excluded from primary safety analysis.  Evaluable echo data available for 83/85 patients at 30 days and 70/85 patients at 6 months for efficacy assessment.  MAEs adjudicated by an independent committee.

    Intervention: T-TEER with TriClip

    Comparator: NA

    Length of follow-up, mean: 6 months

    Patients (N): 85

    Age, years, mean (SD): 77.8 (7.9)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 56 (66)

    Race, n (%): NR

    Diagnosis, n (%):
    TR etiology:
    Functional: 71 (84)
    Degenerative: 10 (12)
    Mixed: 3 (4)
    NYHA Functional Class:
    III or IV: 64 (75)
    TR severity:
    Moderate: 5 (6)
    Severe: 24 (29)
    Massive: 24 (29)
    Torrential: 31 (37)
    EuroSCORE II, mean % (SD): 8.6 (10.9)

    Comorbidities, n (%): See Lurz et al., 2021 above

    Inclusion criteria: Age ≥18 years and ≤90 years; moderate or greater TR (moderate TR must have tricuspid annular diameter ≥40mm and NYHA Class III or IV); NYHA Class II or higher; adequately treated per applicable standards (including OMT); no indication for left-sided or pulmonary valve correction (left-sided heart valve disease or pulmonary stenosis treated at least 30-days prior to study enrollment); eligibility committee supports intervention for TR per benefit-risk analysis and patient is at high risk for TV surgery; TV anatomy suitable for implantation

    Exclusion criteria: Severe uncontrolled hypertension (SBP≥180mmHg and/or DBP≥110mmHg); Doppler echocardiography-determined sPAP>60mmHg; previous TV procedure; mitral regurgitation of moderate-severe or greater severity; CV implantable electronic device (pacemaker or ICD leads) that would inhibit TriClip placement; active endocarditis or rheumatic heart disease or leaflets degenerated from rheumatic disease; MI or known unstable angina within 30 days; PCI within prior 30 days; hemodynamic instability with or without afterload reduction; CVA within 3 months; chronic dialysis; bleeding disorders or hypercoagulable state; active peptic ulcer or active GI bleeding; life expectancy <12 months due to non-cardiac conditions; large coaptation gap (>10mm); LVEF ≤20%; complex anatomy; poor imaging; aortic or TV stenosis; mitral stenosis

    Note: Cardiac surgeon and an echocardiography specialist assessed patients for eligibility, including surgical risk status and TR severity.  Additionally, patients were presented to an independent eligibility committee that reviewed TV anatomy and pertinent medical history to make the final determination regarding eligibility of prospective subjects.

    Primary endpoint:
    TR reduction of ≥1 grade, at 30 days, n/N (%):
    71/83 (86), 97.5% lower confidence limit: 77.3%

    Note: Performance goal for primary efficacy endpoint was 35% with a one-sided 2.5% significance level.

    Other outcomes:
    Reduction to TR severity ≤moderate, BL vs. 6 months, n/N (%): 5/84 (6) vs. 40/70 (57), p<0.0001*** in paired analysis with n=69
    Stratified by BL TR severity, at 6 months, n (%):
    BL severe TR: 18 (86)
    BL massive TR: 12 (50)
    BL torrential TR: 13 (42)
    Breakdown of TR grade, at 6 months, n (%):
    None or trace: 1 (1)
    Mild: 19 (27)
    Moderate: 0 (29)
    Severe: 24 (34)
    Massive: 5 (7)
    Torrential: 1 (1)

    Functional status, NYHA Class I or II, n/N (%):
    BL vs. 30 days: 21/83 (25) vs. 67/84 (80), p<0.0001***, favoring 30 days
    BL vs. 6 months: 21/83 (25) vs. 63/73 (86), p<0.0001***, favoring 6 months

    HF symptoms, KCCQ score, mean (SD) points:
    BL vs. 30 days: 52.2 (NR) vs. 67.2 (NR)
    Difference: 14.2 (SD: 16.7), p<0.0001***, favoring 30 days
    BL vs. 6 months: 52.2 (NR) vs. 72.9 (NR)
    Difference: 18.4 (SD: 21.5), p<0.0001***, favoring 6 months
    Note: Analysis based on N=85 at BL, N=83 at 30 days, and N=72 at 6 months.

    Functional status, 6MWT, mean (SD) meters:
    BL vs. 6 months: 277.6 (137.1) vs. 339.5 (129.8)
    Difference: 54.6 (SD: 111.4), p<0.0003***, favoring 6 months
    Note: Analysis based on N=76 at BL and N=73 at 6 months.
    BL vs. 30 days: 263.4 (NR) vs. 309.9 (NR); p<0.0001***

    QoL, SF-36, mean score (SD):
    BL vs. 3 months:
    Physical component: Difference: 3.81 (8.85), p=0.0002***, favoring 3 months
    Mental component: Difference: 2.85 (11.75), p=0.031*, favoring 3 months
    BL vs. 6 months:
    Physical component: 35.55 (9.63) vs. 42.54 (9.63)
    Difference: 6.30 (10.64), p<0.0001***, favoring 6 months
    Mental component: 44.61 (14.00) vs. 50.08 (10.63)
    Difference: 5.52 (12.95), p=0.0006***, favoring 6 months
    Note: Analysis based on N=85 at BL, N=82 at 30 days, and N=72 at 6 months.

    Procedural outcomes, n (%):
    Implant success with ≥1 grade reduction in TR severity, at discharge, n (%): 76 (91)

    Right heart remodeling and RV function, BL vs. 6 months, mean (SD):
    EROA, cm2: 0.65 (0.29) vs. 0.35 (0.23), p<0.0001***, favoring 6 months
    Regurgitant volume, mL/beat: 51.63 (18.65) vs. 29.10 (14.62), p<0.0001***
    Regurgitant jet area, cm2: 14.29 (6.03) vs. 8.29 (4.76), p<0.0001***
    TR peak jet velocity, cm/s: 270.3 (40.7) vs. 264.2 (45.3), p=0.10
    Vena contracta width, cm: 1.73 (0.63) vs. 0.86 (0.47), p<0.0001***, favoring 6 months
    PISA radius, cm: 0.92 (0.21) vs. 0.64 (0.21), p<0.0001***
    IVC diameter, cm: 2.30 (0.55) vs. 2.06 (0.52), p=0.022*
    Tricuspid annular septolateral diameter, cm: 4.33 (0.59) vs. 4.16 (0.56), p=0.0034**, favoring 6 months
    Mean TV gradient, mmHg: 1.17 (0.64) vs. 2.35 (1.34), p.0001***, favoring BL
    Cardiac output, L/min: 4.22 (1.06) vs. 4.61 (0.91), p=0.15
    Forward LV stroke volume, mL: 61.02 (14.79) vs. 65.03 (12.51), p=0.17
    LVOT VTI, cm: 16.78 (4.94) vs. 16.97 (3.95), p=0.45
    LVEF, %: 59.39 (8.09) vs. 61.12 (7.23), p=0.055
    RV end diastolic dimension, cm: 5.27 (0.67) vs. 4.84 (0.75), p<0.0001***, favoring 6 months
    RV FAC, %: 35.83 (7.39) vs. 38.37 (5.91), p=0.038*, favoring 6 months
    Right atrial volume, mL: 128.04 (53.88) vs. 117.01 (63.28), p=0.032*
    TAPSE, cm: 1.44 (0.31) vs. 1.56 (0.29), p=0.015*, favoring 6 months
    RV global longitudinal strain, %: -13.86 (4.68) vs.
    -14.40 (3.91), p=0.47

    Primary endpoint:
    Composite of MAEs, at 6 months, n/N (%): 3/84 (4), p<0.0001***
    CV mortality: 2 (2)
    MI: 0 (0)
    Stroke: 0 (0)
    New onset renal failure: 1 (1)
    Non-elective CV surgery or TV repair system: 0 (0)
    Device-related AE: 0 (0)

    Note: Performance goal for primary safety endpoint was 39%.  Performance goals for the primary efficacy and safety endpoints were based on MAE rates seen in a previous study with patients at high surgical risk, as well as achieving clinically relevant improvements in outcomes compared with OMT (Nickenig et al., 2017).
    One patient required an additional TV repair system procedure on Day 138 and eventual unplanned surgery due to TV incompetence on Day 144.

    Other safety endpoints, at 6 months, n/N (%):
    All-cause mortality: 4/84 (5)
    Major bleeding: 9/84 (11)
    New onset liver failure: 0 (0)
    New onset atrial fibrillation: 1/84 (1)
    SLDA: 5/72 (7)
    Periprocedural mortality: 0 (0)
    Conversion to surgery: 0 (0)
    Device embolization: 0 (0)
    Tricuspid valve stenosis: 6/65 (9)

    Reference: Naik et al., 2025

    Country: US, Canada, Europe

    Study Design: International randomized, controlled trial in symptomatic patients with severe TR.

    Purpose: To determine the safety and efficacy of T-TEER in patients with transvalvular CIED leads.

    Funding Source: Abbott

    Qualitya: NA
    No formal quality assessment was performed due to single-arm study design.

    Intervention: T-TEER with TriClip

    Comparator: CIED positive vs. CIED negative

    Length of follow-up: 30 days and 1 year

    Patients (N): 465 total, 98 in the CIED positive group

    Age, years, mean (SD): CIED+: 80.2 (8.6); CIED-: 78.3 (7.6)

    Sex, female, n (%): CIED+: 58 (59.2); CIED-: 223 (60.1)

    Race, n (%): NR

    Diagnosis, n (%): NR

    Inclusion criteria: For patients with CIED leads, eligibility was determined by an independent eligibility committee prior to inclusion in the randomized or single-arm cohorts.
    Note: The committee considered factors like lead location, lead mobility, lead-leaflet interaction, and TR jet location on a case-by-case basis when making this determination. It is unknown how T-TEER would have performed in patients with CIED leads who were screen-failed by the eligibility committee.

    Exclusion criteria: CIED patients screen-failed bv the eligibility committee

    TR reduction to moderate or severe, %: CIED+: 88; CIED-: 87

    Sustained TR reduction at 1 year, %: CIED+: 81; CIED-: 84

    Significant improvement in QoL (KCCQ) at 1 year: CIED+: 18.7 (22.6); CIED-: 16.8 (22.6)

    NYHA improvement to class I or II at 30 days, %: CIED+: 85; CIED-: 87

    Length of stay in hospital (days) (SD): CIED+: 2 (3); CIED-: 1.6 (1.5)
    Note: p= .98

    MAE through 30 days, n (%):CIED+: 1 (1.0); CIED-: 4 (1.1)

    Major bleeding through 30 days, n (%):CIED+: 3 (3.1); CIED-: 11 (3.0)

    Tri.Fr

    Reference: Donal et al., 2025

    Country: France, Belgium

    Study Design: Prospective, randomized (1:1) trial evaluating T-TEER + OMT vs OMT alone in adult patients with severe, symptomatic TR.

    Purpose: To evaluate the efficacy of T-TEER + OMT vs OMT alone in patients with severe, symptomatic TR.

    Funding Source: French Ministry of Health

    Qualitya: NA

    Intervention: T-TEER with TriClip + OMT

    Comparator: OMT alone

    Length of follow-up: 1 year

    Patients (N): 300

    Age, years, mean (SD): 78.3 (6)

    Sex, female, n (%): 191 (63.7)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA II: 170 (56.7)
    NYHA III-IV: 127 (42.3)

    Comorbidities, n (%):
    Atrial fibrillation: 285 (95)
    Atrial arrhythmia on ECG: 233 (77.7)
    Hypertension: 208 (69.3)
    Dyslipidemia: 123 (41)
    Stroke or TIA: 44 (14.7)
    Diabetes: 48 (16)
    Peripheral vascular disease: 28 (9.3%)
    Paced rhythm on ECG: 21 (7)
    Chronic obstructive pulmonary disease: 20 (6.7)
    Prior ST-segment elevation myocardial infarction: 14 (4.7)

    Inclusion criteria: All patients with severe, symptomatic tricuspid regurgitation despite stable (=30 days) guideline-directed OMT for heart failure were considered eligible if they were free from other cardiovascular conditions requiring intervention.
    Note: Severity of TR and anatomical suitability for T-TEER were evaluated and confirmed by a central echocardiography laboratory (independent and blinded).

    Composite clinical end point at 1 year:
    T-TEER + OMT: 74.1% had improvement.
    OMT: 40.6% had improvement
    Note: Composite end point was comprised of changes in NYHA class, patient global assessment, and occurrence of major cardiovascular events.

    KCCQ at 1 year, mean:
    T-TEER + OMT: 54 at baseline, 69.9 at 1y
    OMT alone: 54 at baseline, 55.5 at 1y
    Note: Absolute difference at 1y was 14.5, P<0.001.

    NR

    bRIGHT Study

    Reference: Lurz et al., 2024

    Country: Germany, France, Spain

    Study Design: Prospective, multi-center (26 sites), open-label, single-arm, post-market registry
    NCT04483089

    Purpose: To report the 1-year clinical outcomes of subjects treated by T-TEER with the TriClip system in a contemporary, real-world setting.

    Funding Source: Abbott (Santa Clara, US)

    Qualityα: No formal quality assessment performed due to observational, single-arm study design.

    Notes: NA

    Intervention: T-TEER with the TriClip system

    Comparator: NA

    Length of follow-up, mean: Patients followed up with at 1 year.

    Patients (N): 511

    Age, years, mean (SD): 79 (7)

    Age ≥ 65, n (%): NR

    Sex, female, %: 56

    Race, n (%): NR

    Diagnosis, %:
    NYHA functional class III or IV: 80
    Baseline TR Severity:
    Severe: 10
    Massive: 61
    Torrential: 27

    Comorbidities, n (%):
    Chronic renal disease: 40

    Inclusion criteria: See Lurz et al., 2023.

    Exclusion criteria: See Lurz et al., 2023.

    TR grade, moderate or less, %:
    30 days: 85, difference from baseline, p<0.0001
    1 year: 81, difference from 30 days, p=0.69
    N=317

    No significant difference in TR grade at 30 days and 1 year between sites that completed ≤15 procedures vs. >15 procedures

    Improvement in KCCQ-Overall summary, mean (SD):
    30 days: no significant difference from 1 year
    1 year: 19 (26), difference from baseline, p<0.0001

    No significant difference in average KCCQ-Overall summary score at 1 year between sites that completed ≤15 procedures vs. >15 procedures

    NYHA class I or II, baseline vs. 1 year, %: 21 vs. 75 (p<0.0001) [N=365]

    Note: Missing data at 1 year were due to death (n=79), withdrawal (n=42), visit not completed (n=12), and TR not measurable (n=59).

    Kaplan-Meier survival at 1 year, OR (95% CI):
    Baseline KCCQ: 0.73 (0.55, 0.96), p=0.022
    Site experience: 0.87 (0.68, 1.12), p=0.293
    RV TAPSE: 0.76 (0.55, 1.04), p=0.085
    Alanine transaminase: 1.06 (0.81, 1.39), p=0.659
    Aspartate transaminasse: 1.26 (1.00, 1.58), p=0.047
    Moderate or less residual TR: 0.32 (0.19, 0.56), p<0.001
    Female: 0.55 (0.33, 0.91), p=0.02
    Systolic pulmonary artery pressure: 1.04 (0.80, 1.35), p=0.784
    Serum creatinine: 1.85 (1.42, 2.39), p<0.001
    LVEF: 0.71 (0.56, 0.91), p=0.007

    Heart failure hospitalization rate, events/patient-year, 1 year pre- vs. post-device: 0.57 vs. 0.28, p<0.0001

    AEs, 30 days, n (%):
    Major bleeding: 36 (7.0)
    Device embolization: 0 (0)
    Single leaflet device attachment: 18 (3.5)
    Non-elective cardiovascular surgery for device-related adverse event: 1 (0.2)
    TV reintervention: 1 (0.2)
    TV reoperation: 2 (0.4)
    New pacemaker implantation: 0 (0)
    New onset renal failure: 7 (1.4)
    All-cause mortality: 5 (1.0)
    Cardiovascular mortality: 4 (0.8)

    AEs, 1 year, n (%):
    Major bleeding: 55 (10.8)
    Device embolization: 0 (0)
    Single leaflet device attachment: 20 (3.9)
    Non-elective cardiovascular surgery for device-related adverse event: 1 (0.2)
    TV reintervention: 18 (3.5)
    TV reoperation: 6 (1.2)
    New pacemaker implantation: 4 (0.8)
    New onset renal failure: 28 (5.5)
    All-cause mortality: 72 (15.1)
    Cardiovascular mortality: 45 (8.8)

    Note: Major bleeding was defined as Bleeding Academic Research Consortium Type 3A.

    Reference: Goebel et al., 2025

    Country: Europe

    Study Design: Prospective, single-arm, open-label, multicenter, post-market registry (26 sites).

    Purpose: To examine the effectiveness and safety of T-TEER in patients with endocardial leads.

    Funding Source: NR

    Qualitya: NA
    No formal quality assessment was performed due to observational, single-arm study design.

    Intervention: T-TEER for patients with endocardial leads

    Comparator: T-TEER with no leads

    Length of follow-up, mean: 30 days

    Patients (N): 511 (110 with leads)

    Age, years, mean (SD):
    Lead: 78.7 (7.8)
    No lead: 79 (7.0)
    Combined: 78.9 (7.1)

    Age ≥ 65, n (%): NR

    Sex, female (%):
    Lead: 43.6
    No lead: 59.1
    Total: 55.8

    Race, n (%): NR

    Diagnosis, %:
    NYHA III/IV:
    Lead: 82.6
    No lead: 79.1
    Total: 79.8

    Comorbidities, %:
    Hypertension: Lead: 87.3; No lead: 86.5
    Atrial fibrillation: Lead: 86.4; No lead: 86.3
    Renal disease: Lead: 48.2; No lead: 37.2
    Diabetes: Lead: 25.5; No lead: 21.4
    Chronic obstructive pulmonary disease:
    Lead: 15.5; No lead: 12.5
    Peripheral vascular disease: Lead: 7.3; No lead: 12.0
    Prior stroke: Lead: 7.3; No lead: 8.2
    Prior MI: Lead: 13.6; No lead: 9.5

    Inclusion criteria: See Lurz et al., 2023. Subset of 110 patients who had endocardial leads from CIEDs crossing the tricuspid valve.

    Exclusion criteria: See Lurz et al., 2023.

    KCCQ-OS, mean change (SD):
    Lead: 20.14 (24.02)
    No lead: 18.42 (22.48)
    Notes: p<0.001 for both groups

    NYHA class I/II, baseline vs. 30 days, %:
    Lead: 17 vs. 75
    No lead: 21 vs. 80
    Notes: p<0.0001 for both groups

    Major adverse events, % (n):
    Cardiovascular mortality: Lead: 0 (0); No lead 1 (4)
    MI: Lead: 0 (0); No lead: 0 (0)
    Stroke: Lead: 0 (0); No lead: 0 (0)
    New-onset renal failure: Lead: 0.9 (1); No lead: 1.5 (6)
    Major bleeding: Lead: 6.4 (7); No lead: 7.5 (30)

    Reference: Donal et al., 2024

    Country: France, Spain, Germany

    Study Design: Prospective, multi-center (24 sites), open-label, single-arm, post-market registry
    NCT04483089

    Purpose: To characterize the TV and coaptation gap in patients selected for t-TEER in a contemporary post-market setting

    Funding Source: Abbott

    Qualityα: No formal quality assessment performed due to observational, single-arm study design.

    Notes: NA

    Intervention: T-TEER with a TriClip or TriClip G4 device

    Comparator: NA

    Length of follow-up, mean: Patients were followed for 30 days post-procedure

    Patients (N): 135

    Age, years, mean (SD): 78 (9)

    Age ≥ 65, n (%): NR

    Sex, female (%): 50

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA I/II: 25 (19)

    Comorbidities, n (%):
    Hypertension: 112 (83)
    Atrial fibrillation: 111 (82)
    Renal disease: 55 (41)
    Diabetes: 29 (22)

    Inclusion criteria: See Lurz et al., 2023.

    Exclusion criteria: See Lurz et al., 2023.

    Procedural outcomes, n (%):
    Implant success: 130 (99), N=131
    Acute procedural success: 111 (91), N=122

    30-day TR reduction, number of grades, mean (SD), N:
    Coaptation gap:
    < 7 mm: 2.2 (1.2), 25
    7-10 mm: 2.5 (1.3), 28
    > 10 mm: 2.3 (1.5), 24

    Degree of tethering:
    Normal leaflet motion: 2.3 (1.4), 11
    Mild restriction: 2.3 (1.5), 59
    Moderate restriction: 2.6 (0.8), 7
    TV morphology:
    Type 1: 2.3 (1.4), 11
    Type 2: 2.3 (1.5), 59
    Type 3b: 2.6 (0.8), 7
    Other: 2.0 (1.4), 4

    30-day moderate or less TR, n (%), N:
    Coaptation gap:
    < 7 mm: 19 (73.1), 26
    7-10 mm: 22 (78.6), 22
    > 10 mm: 16 (59.3), 27
    Degree of tethering:
    Normal leaflet motion: 9 (75), 12
    Mild restriction: 39 (63.8), 61
    Moderate restriction: 5 (71.4), 7
    TV morphology:
    ype 1: 37 (64.9), 57
    Type 2: 5 (83.3), 6
    Type 3b: 11 (78.6), 14
    Other: 4 (100), 4

    Events occurring within 30 post-procedure days, n (%), N:
    Single-leaflet device attachment: 5 (3.8), 131
    Embolization: 0
    MAE (new-onset renal failure): 1 (0.8), 131

    Reference: Lurz et al., 2023 (bRIGHT 30-day outcomes)

    Country: Europe

    Study Design: Prospective, multi-center (26 sites), open-label, single-arm, post-market registry, NCT04483089

    Purpose: To evaluate safety and effectiveness in non-selected patients with severe TR treated with TriClip and TriClip G4 TEER systems in a real-world, contemporary setting

    Funding Source: NR

    Qualityα: NA
    No formal quality assessment was performed due to observational, single-arm study design.

    Notes: Echocardiographic assessment performed at independent core lab, except for analysis of TR grades at BL and/or post-procedurally.  All MAEs adjudicated by an independent events committee.  Patients who had an attempted procedure were included in the analysis population upon femoral vein puncture.

    Intervention: T-TEER using TriClip or TriClip G4

    Comparator: NA

    Length of follow-up, mean: Patients were followed for 30 days post-procedure

    Patients (N): 511

    Age, years, mean (SD): 78.9 (7.1)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 286 (56)

    Race, n (%): NR

    Diagnosis, n (%):
    TR severity:
    Moderate: 10 (2.0)
    Severe: 51 (10.0)
    Massive: 313 (61.3)
    Torrential: 137 (26.7)
    NYHA Class:
    III or IV: 409 (80)
    TR etiology:
    Functional: 460 (90)
    Atrial TR: 388 (76)
    Ventricular TR: 123 (24)

    Comorbidities, n (%):
    Hypertension: 443 (86.7)
    Atrial fibrillation: 441 (86.3)
    Mitral regurgitation ≥moderate: 31 (6.0)
    Prior aortic intervention: 47 (9.2)
    Prior mitral intervention: 137 (26.8)
    Prior CABG: 59 (11.5)
    Diabetes: 114 (22.3)
    Chronic renal disease: 202 (39.5)
    COPD: 67 (13.1)
    Peripheral vascular disease: 56 (11.0)
    Prior stroke: 41 (8.0)
    PPM/ICD: 115 (22.5)
    Prior MI: 53 (10.4)

    Inclusion criteria: Symptomatic patients with severe TR despite medical therapy; ≥18 years old; eligible to receive T-TEER per the currently approved intended use and target patient population; not be a participant in another clinical study that could impact follow-up or results

    Exclusion criteria: Severe pulmonary hypertension (sPAP>60 mmHg); severe mitral regurgitation

    Primary endpoint:
    Acute procedural success (survival to discharge with successful implantation of device and resulting TR reduction ≥1 grade), at discharge, n (%): 184 (92)
    Note: Evaluated in the primary analysis population of the first 200 patients.

    Other endpoints:
    Implant success (successful delivery and deployment of device): 504 (99)

    Procedural success (implant success with resulting TR reduction ≥1 grade at discharge or 30 days if discharge TR grade unavailable), n (%): 451 (91)
    Note: 496 patients had readable TR severity.

    Reduction to TR severity ≤ moderate, n/N (%):
    At BL vs. discharge: 10/479 (2) vs. 383/479 (80), p<0.0001***, favoring discharge
    At BL vs. 30 days: 8/389 (2) vs. 300/389 (77), p<0.0001***, favoring discharge
    Stratified by BL TR severity, at 30 days:
    Severe: 35/37 (95)
    Massive: 198/242 (82)
    Torrential: 61/103 (59)
    BL torrential vs. BL massive/severe, at discharge:
    Univariate analysis: OR: 0.31 (95% CI: 0.19 to 0.50), p<0.0001***, favoring massive/severe
    Multivariate analysis: OR: 0.371 (95% CI: 0.223 to 0.617), p=0.0001***, favoring massive/severe

    No reduction or worse TR severity, at 30 days: 6% across all BL severe, massive, and torrential patient groups

    Note: N=479 patients had evaluable TR severity at both BL and discharge (n=2 death, n=2 withdrawal, n=15 visit not done, n=13 TR not measurable).  N=389 patients had evaluable TR severity at both BL and 30 days (n=17 death, n=17 withdrew consent, n=57 visit not done, n=9 TR not measurable at BL, n=22 TR not measurable at 30 days).

    Functional capacity, NYHA Class I or II, BL vs. 30 days, n/N (%): 93/446 (20) vs. 368/446 (79), p<0.0001***, favoring 30 days

    QoL, increase in KCCQ score, at 30 days, mean (SD) points: 19 (23), p<0.0001***
    Increase of ≥15 points, n/N (%): 236/420 (56.2)
    Increase of ≥20 points, n/N (%): 203/420 (48.3)
    Stratified by 30-day TR severity, mean increase in score, points:
    ≤Moderate (n=287): 20
    ≥Severe (n=85): 12

    Echocardiographic parameters, BL vs. 30 days, mean (SD):
    EROA, cm2: 0.80 (0.51) vs. 0.42 (0.38), p<0.0001***, favoring 30 days
    Regurgitant volume, mL/beat: 59.15 (28.38) vs. 31.96 (20.89), p<0.0001***, favoring 30 days
    Regurgitant jet area, cm2: 10.41 (5.34) vs. 6.07 (4.74), p<0.0001***, favoring 30 days
    Vena contracta width, cm: 0.85 (0.36) vs. 0.50 (0.36), p<0.0001***, favoring 30 days
    PISA radius, cm: 0.82 (0.22) vs. 0.56 (0.34), p<0.0001***, favoring 30 days
    IVC diameter, cm: 2.31 (0.66) vs. 2.09 (0.71), p=0.0059**, favoring 30 days
    RVEDD, cm: 4.63 (0.92) vs. 4.28 (0.86), p<0.0001***, favoring 30 days
    Tricuspid annular diameter, cm: 4.54 (0.76) vs. 4.27 (0.73), p<0.0001***, favoring 30 days
    Right atrial volume, mL: 151.66 (70.46) vs. 4.27 (0.73), p<0.0001***, favoring 30 days
    RVFAC, %: 39.4 (8.4) vs. 38.9 (8.6), p=0.5929
    TAPSE, cm: 1.70 (0.44) vs. 1.69 (0.48), p=0.2035
    LVEF, %: 55.79 (10.58) vs. 57.73 (10.13), p=0.0114*, favoring 30 days

    MAEs, at 30 days, n/N (%): 14/511 (2.5)
    CV mortality: 4 (0.8)
    MI: 0 (0)
    Stroke: 2 (0.4)
    New onset renal failure: 7 (1.4)
    Endocarditis requiring surgery: 0 (0)
    Non-elective CV surgery for device-related AE: 1 (0.2)

    Other safety endpoints, at 30 days, n (%):
    All-cause mortality: 5 (1.0)
    TV re-intervention: 1 (0.2)
    TV re-operation: 2 (0.4)
    Major bleeding: 37 (7.2)
    Device embolization: 0 (0)
    Device thrombosis: 0 (0)
    New pacemaker implantation: 0 (0)
    SLDA: 17 (3.8)

    Note: Safety endpoints assessed in N=511 patients.

    Bonn Registry Studies

    Reference: Tanaka et al., 2024

    Country: Germany

    Study Design: Retrospective analysis of prospective registry

    Purpose: To evaluate the post-procedural change in RV function and investigated the association of RV function at baseline and its post-procedural changes with clinical outcomes in patients undergoing T-TEER

    Funding Source: NR

    QualityαNo formal quality assessment performed due to prospective registry design.

    Notes: All clinical events, including hospitalization due to heart failure, were independently adjudicated by the local heart team based on the criteria of the Valve Academic Research Consortium 3.20 The occurrence of clinical events were recorded from admission and outpatient medical records, telephone interviews, or documentation from the referring general practitioners.

    Intervention: T-TEER using either the MitraClip or TriClip system or PASCAL system

    Comparator: NA

    Length of follow-up, median (IQR), days: 421 (237-786)

    Patients (N): 204
    Device, %:
    TriClip: 59.8
    PASCAL: 27.0
    MitraClip: 13.2

    Age, years, mean (SD): 78.9 (6)

    Age ≥ 65, n (%): NR

    Sex, female, n (%): 108 (52.9)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA class III or IV: 159 (77.9)
    TR severity:
    3+: 105 (51.5) (Severe)
    4+: 82 (40.2) (Massive)
    5+: 17 (8.3) (Torrential)

    Comorbidities, n (%):
    Diabetes: 47 (23.0)
    Hypertension: 172 (84.3)
    CAD: 107 (52.5)
    Previous myocardial infarction: 45 (22.1)
    Atrial fibrillation: 193 (94.6)
    COPD: 44 (21.6)

    Inclusion criteria: Consecutive patients with symptomatic TR who underwent T-TEER from June 2015 to April 2022

    Exclusion criteria: NR

    Primary endpoint:
    Risk of composite of mortality or hospitalization due to heart failure within 1 year:
    Baseline RV fractional area change (RVFAC) < 35% vs. RVFAC ≥ 35%, %: 46.8% vs. 23.8%; p=0.006
    RV responder, HR (95% CI): 1.06 (0.60-1.86), p=0.84
    Baseline RVFAC < 35, HR (95% CI):
    RV responders: 0.35 (0.14-0.89), p=0.028
    Baseline RVFAC ≥ 35, HR (95% CI):
    RV responders: 1.44 (0.71–2.90), p=0.31
    Low TAPSE/sPAP at baseline and decreased TAPSE at 3-month follow-up [reference: high and increased TAPSE/SPAP]: 5.37 (2.12-13.61), p<0.001
    Low TAPSE/SPAP (< 0.317 mm/mmHg) at baseline: 2.27 (1.30-3.99), p=0.004
    Residual RV dysfunction, i.e., RVFAC < 35% at baseline and follow-up: 3.92 (1.93-7.93), p<0.001
    RV non-responders with baseline RVFAC ≥35%, 3 months vs. 1 year, mean (SD): 38.5 (8.8%) vs. 40.7 (11.5%), p=0.77

    Multivariable Cox proportional analysis, HR (95% CI):
    Baseline RVFAC < 35:
    aHR [reference: RV responders with baseline RVFAC ≥35%], (95% CI): 2.55 (1.12–5.83), p=0.027

    Other endpoints:
    Follow-up echocardiography, median (IQR), days: 90 (58-95)

    RV fractional area change, Baseline vs. Follow-up, mean (SD): 44.0 (9.9) vs. 40.1 (10.2), p<0.001
    No significant changes from 3-month follow-up to 1 year follow-up (p=0.38).

    Procedural success, n (%): 161 (78)

    Reduction in TR severity, grade, median (IQR): 2 (1-2)

    Note: In a small sample of patients with RV dysfunction at baseline (n=45), RV responder was predicted by a smaller RV diameter and a greater reduction in TR severity (aOR (95% CI): 0.89 (0.80–0.99), p=0.038; and 1.75 (1.07–7.68), p=0.037; respectively).

    NR

    Reference: Vogelhuber et al., 2024

    Country: Germany

    Study Design: Retrospective analysis of prospective cohort

    Purpose: To assess the safety profile of T-TEER in patients with RV dysfunction.

    Funding Source: None

    QualityαNo formal quality assessment performed due to prospective registry design.

    Notes: NA

    Intervention: T-TEER with TriClip/MitraClip or PASCAL

    Comparator: NA

    Length of follow-up, mean (IQR), days: 374 (185-728)

    Patients (N): 262
    Normal RV function: 218
    RV dysfunction: 44

    Device, n (%):
    TriClip: 95 (36.3)
    PASCAL: 71 (27.1)
    MitraClip: 96 (36.6)

    Age, years, mean (SD): 78.9 (6.7)

    Age ≥ 65, n (%): NR

    Sex, female, n (%): 134 (51.2)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA functional class IV: 39 (14.9)
    TR severity:
    3+: 139 (53.1) (Severe)
    4+: 97 (37.0) (Massive)
    5+: 26 (9.9) (Torrential)

    Comorbidities, n (%):
    Arterial hypertension: 220 (84.0)
    Diabetes: 61 (23.3)
    Atrial fibrillation/flutter: 244 (93.1)
    History of myocardial infarction: 62 (23.7)
    History of stroke: 28 (10.7)
    CAD: 140 (53.4)
    Prior pacemaker/ICD/CRT: 81 (30.9) 64
    Peripheral vascular disease: 88 (33.6)

    Inclusion criteria: Consecutive patients with symptomatic TR who underwent T-TEER from July 2015 to December 2021 in the University Hospital Bonn

    Exclusion criteria: NR

    Primary endpoint:
    30-day mortality, Normal RV vs. RV Dysfunction, n (%): 7 (3.2) vs. 1 (2.3), p=0.99

    Secondary endpoints:
    Implant success, Normal RV vs. RV Dysfunction, n (%): 206 (94.9) vs. 40 (90.9), p=0.49

    Procedural success, Normal RV vs. RV Dysfunction, n (%): 197 (90.8) vs. 39 (88.6), p=0.59

    TR reduction to ≤2+ at discharge, Normal RV vs. RV Dysfunction, %: 76.4 vs. 70.5
    Note: the authors noted that the two groups were comparable for TR reduction.

    Charges in TAPSE, Baseline vs. Post-Procedure, mean (SD):
    Normal RV (n=205): 19.0 (4.8) vs. 17.9 (4.5), p=0.001
    RV Dysfunction (n=42): 13.2 (2.3) vs. 15.3 (4.7), p=0.011

    Changes in RVFAC, Baseline vs. Post-Procedure, mean (SD):
    Normal RV (n=205): 46.2 (8.1) vs. 40.3 (9.7), p<0.001
    RV Dysfunction (n=41): 29.6 (4.1) vs. 31.6 (8.3), p=0.14

    Other endpoints:
    In-hospital mortality, Normal RV vs. RV Dysfunction, n (%): 5 (2.3) vs. 1 (2.3), p=0.99

    2-year outcomes, Normal RV vs. RV Dysfunction:
    Follow-up, days, median (IQR): 374 (185-728)
    Mortality, %: 27 vs. 56.3, P<0.001
    Cardiovascular death, %: 14.1 vs. 39.0, P<0.001
    Heart failure rehospitalization, %: 29.9 vs. 49.1, P=0.007

    Complications, Normal RV vs. RV Dysfunction, n (%):
    Periprocedural death: 0 vs. 0, p=0.99
    Conversion to surgery: 0 vs. 0, p=0.99
    Pericardial tamponade: 3 (1.4) vs. 0, p=0.99
    Major bleeding: 12 (5.4) vs. 3 (6.8), p=0.87
    Multiple blood transfusion: 13 (5.9) vs. 5 (11.8), p=0.28
    Pneumonia: 4 (1.8) vs. 3 (6.8), p=0.09
    Acute kidney injury: 34 (15.6) vs. 6 (13.6), p=0.99
    Stroke: 0 vs. 0, p=0.99

    TriValve Registry Studies

    Reference: Coisne et al., 2023

    Country: US, Italy, Germany, Canada, Spain, France, Switzerland

    Study Design: Prospective registry, multi-center study with subgroup analysis (TriValve NCT03416166)

    Purpose: To evaluate the association between the mean TV gradient and clinical outcomes among patients who underwent T-TEER for significant TR.

    Funding Source: NR

    Qualityα: No formal quality assessment was performed due to this being a registry study.

    Notes: NA

    Intervention T-TEER with MitraClip, TriClip, and PASCAL

    Comparator: NA

    Length of follow-up, days, median (IQR): 174 (43-364)

    Patients (N): 308
    Quartiles for TV gradient at discharge:
    Q1, 0 to 1.1 mm Hg, n: 77
    Q2, 1.2 to 2.0 mm Hg, n: 115
    Q3, 2.1 to 3.0 mm Hg, n: 65
    Q4, 3.1 to 16.2 mm Hg, n: 51

    Age, years, mean (SD): 76.4 (9.2)

    Age ≥ 65, n (%): NR

    Sex, female, n (%): 172 (55.8)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA functional class III-IV: 277 (91.1)
    TR etiology:
    Functional: 266 (86.9)
    Degenerative: 15 (4.9)
    Mixed: 20 (6.5)
    Other: 5 (1.6)
    TR severity:
    2/4: 11 (3.6) (Moderate)
    3/4: 142 (46.3) (Severe)
    4/4: 154 (50.2) (Massive/Torrential)

    Comorbidities, n (%):
    Diabetes: 85 (27.7)
    COPD: 71 (23.1)
    Atrial fibrillation: 189 (61.8)
    Prior myocardial infarction: 49 (15.9)
    Pacemaker/ICD: 87 (28.3)
    Ascites: 63 (22.3)
    Peripheral edema: 207 (72.9)
    Previous RV failure: 185 (68.2)
    Previous left-side valve intervention: 68 (22.1)

    Inclusion criteria: Symptomatic heart failure and significant TR ≥ 2.  Patients underwent T-TEER from August 2015 to March 2022.

    Exclusion criteria: NR

    Primary endpoint:
    All-cause mortality and heart failure hospitalization at 1 year, n (%): 63 (20.4)

    By TV gradient quartile:
    Q1 35%, Q2 30%, Q3 40%, and Q4 34%, P=0.63

    Multivariate aHR (95% CI):
    Q4, reference Q1-Q3: 0.97 (0.47-1.97), p=0.93
    Age, per 1-year increase: 1.02 (0.98-1.05), p=0.32
    Male: 1.18 (0.69-2.02), p=0.54
    Atrial fibrillation: 0.72 (0.43-1.23), p=0.24
    Diabetes mellitus: 1.75 (1.02-3.02), p=0.04
    COPD: 0.94 (0.52-1.71), p=0.84
    Post-TEER TR >2+: 2.20 (1.17-4.11), p=0.01

    Secondary endpoints:
    All-cause mortality at 1 year, n (%): 34 (11.0)
    By TV gradient quartile:
    Q1 27%, Q2 16%, Q3 18%, and Q4 20%, P=0.58

    Multivariate aHR, (95% CI):
    Q4, reference Q1-Q3: 0.80 (0.27-2.31), p=0.67
    Age, per 1-year increase: 1.04 (0.99-1.10), p=0.09
    Male: 0.99 (0.47-2.11), p=0.99
    Atrial fibrillation: 0.31 (0.14-0.71), p=0.005
    Diabetes mellitus: 2.11 (1.02-4.40), p=0.04
    COPD: 0.56 (0.21-1.49), p=0.24
    Post-TEER TR >2+: 2.60 (1.07-6.32), p=0.04

    Heart failure hospitalization, n (%): 48 (15.6)
    By TV gradient quartile:
    Q1 28%, Q2 21%, Q3 36%, and Q4 31%, P=0.44

    Multivariate aHR (95% CI):
    Q4, reference Q1-Q3: 1.13 (0.53-2.42), p=0.75
    Age, per 1-year increase: 1.01 (0.97-1.05), p=0.56
    Male: 1.24 (0.67-2.26), p=0.49
    Atrial fibrillation: 0.84 (0.46-1.51), p=0.55
    Diabetes mellitus: 2.31 (1.27-4.22), p=0.006
    COPD: 1.03 (0.53-1.98), p=0.94
    Post-TEER TR >2+: 2.70 (1.38-5.28), p=0.004

    NYHA class III or IV:
    No difference between patients in Q1 and Q4 before TEER, at 30 days (P=0.84), and at the last follow-up (P=0.63).

    Other endpoints:
    Duration of procedure, min, Q1 vs. Q2 vs. Q3 vs. Q4, mean (SD):
    114.8 (45.3) vs. 114.9 (39.9) vs. 140.4 (70.8) vs. 135.5 (57.3), p=0.01

    Delta TV gradient, mm Hg, Q1 vs. Q2 vs. Q3 vs. Q4, mean (SD):
    0.06 (0.19) vs. 0.74 (0.47) vs. 1.52 (0.66) vs. 2.93 (1.13), p<0.01

    Delta TR severity (post- vs. pre-), Q1 vs. Q2 vs. Q3 vs. Q4, mean (SD):
    0: 3 (4.0) vs. 7 (6.1) vs. 7 (10.8) vs. 5 (10.0)
    1: 27 (36.0) vs. 32 (28.1) vs. 17 (26.2) vs. 16 (32.0
    2: 28 (37.3) vs. 54 (47.4) vs. 30 (46.2) vs. 18 (36.0)
    3: 17 (22.7) vs. 21 (18.4) vs. 10 (15.4) vs. 11 (22.0)
    4: 0 (0.0) vs. 0 (0.0) vs. 1 (1.5) vs. 0 (0.0), p=0.53

    NR

    Reference: Russo et al., 2023

    Country: US, Italy, Germany, Canada, Spain, France, Switzerland

    Study Design: Prospective multi-center registry subgroup analysis (TriValve NCT03416166)

    Purpose: To investigate clinical and echocardiographic characteristics, and procedural and clinical outcomes of patients with atrial secondary TR (ASTR) vs. ventricular secondary TR (VSTR) receiving T-TEER

    Funding Source: NR

    Qualityα: No formal quality assessment was performed due to this being a registry study.

    Notes: NA

    Intervention: T-TEER with MitraClip, TriClip, and PASCAL

    Comparator: NA

    Length of follow-up, mean: Follow-up was conducted at 12 months.

    Patients (N):
    ASTR: 65
    VSTR: 233

    Age, years, ASTR vs. VSTR, mean (SD): 77 (8) vs. 77 (9)

    Age ≥ 65, n (%): NR

    Sex, ASTR vs. VSTR, female, n (%):
    44 (68) vs. 126 (54)

    Race, n (%): NR

    Diagnosis, ASTR vs. VSTR:
    NYHA class III/IV, %: 56 (86) vs. 214 (92)
    TR grade, %:
    2+: 3 vs. 3
    3+: 45 vs. 45
    4+: 52 vs. 52

    Comorbidities, n (%):
    Atrial fibrillation: 65 (100) vs. 127 (55)
    Diabetes: 23 (35) vs. 57 (24)
    Prior CAD: 15 (23) vs. 74 (32)
    COPD: 13 (17) vs. 41 (18)

    Inclusion criteria: All patients undergoing T-TEER.

    Exclusion criteria: Patients not fulfilling the indications for T-TEER.

    Primary endpoint, ASTR vs. VSTR:
    Procedural success, n (%):
    52 (80) vs. 193 (83), p=0.56

    Survival, %:
    91% vs. 72%, log-rank p=0.02

    Note: The survival was defined as the time from the date of T-TEER until death due to any cause.

    Multivariate analysis for mortality risk prediction, HR (95% CI):
    Group VSTR: 2.94 (0.97-8.94), p=0.057
    Age≥75 years: 1.66 (0.67–4.12), p=0.27
    Elevated NT-proBNP: 1.14 (0.42–3.09), p=0.78
    TAPSE <17 mm: 1.89 (0.86–4.16), p=0.11
    High-dose diuretics: 2.11 (0.99–4.47), p=0.051
    Acute procedural success: 0.41 (0.17–0.96), p=0.04

    Other endpoints, ASTR vs. VSTR:
    Procedural time, min, mean (SD): 118 (52) vs. 129 (58), p=0.20
    Length of stay, days, mean (SD): 3 (3) vs. 4 (5), p= 0.10
    TR≤2+, %: 77 vs. 85

    Complications, ASTR vs. VSTR:
    Device delivery failure, n (%): 3 (5) vs. 3 (1), p=0.11
    Conversion to surgery, %: 1 vs. 1, p=0.46
    Stroke, %: 3 vs.1, p=0.07
    MI, %: 0 vs. 0
    Infections, %: 4 vs. 6, p=0.48

    Other Prospective Studies

    Reference: Dannenberg et al., 2024

    Country: Austria, Germany

    Study Design: Single-arm interventional study with subgroup analysis

    Purpose: To elaborate (i) the number of patients with primary leaflet defects in an all-comer cohort of T-TEER patients, (ii) their clinical characteristics compared with patients with secondary TR, and (iii) the feasibility of T-TEER and the post-procedural reduction of TR compared with patients with secondary TR.

    Funding Source: An unrestricted grant from the Austrian Science Foundation (KLI 818-B).

    Qualityα: No formal quality assessment performed due to single-arm study design

    Notes: The study authors referred to this as a post hoc analysis of a prospective cohort, but it appeared to be an interventional study.

    Intervention: T-TEER using Tri-/MicraClip or PASCAL

    Comparator: NA

    Length of follow-up, mean: NA

    Patients (N): 339
    Primary TR: 44
    Secondary TR: 295

    Age, years, mean (SD):
    Primary TR: 79 (8)
    Secondary TR: 78 (8)

    Age ≥ 65, n (%): NR

    Sex, female, n (%):
    Primary TR: 29 (66)
    Secondary TR: 152 (52)

    Race, n (%): NR

    Diagnosis, Primary vs. Secondary TR:
    TR grade, median (IQR): 3 (1) vs. 4 (1)
    NYHA class ≥ III, %: 90 vs. 92

    Comorbidities, Primary vs. Secondary TR, n (%):
    CAD: 16 (36) vs. 143 (49)
    Previous MCI: 4 (9) vs. 31 (11)
    Previous PCI: 7 (18) vs. 90 (32)
    Previous coronary artery bypass graft: 4 (9) vs. 51 (17)
    Previous valve surgery: 6 (14) vs. 43 (15)
    Previous valve intervention: 2 (5) vs. 32 (11)
    Atrial fibrillation: 37 (84) vs. 266 (90)
    CIED: 9 (21) vs. 105 (36)
    Stroke: 5 (11) vs. 39 (13)
    COPD: 5 (11) vs. 59 (20)
    Renal failure: 26 (59) vs. 187 (63)
    Dialysis: 0 (0) vs. 8 (3)
    Cerebral artery occlusive disease: 0 (0) vs. 27 (9)
    Peripheral artery disease: 3 (7) vs. 33 (11)
    Hypertension: 3 (7) vs. 33 (11)
    Diabetes: 6 (14) vs. 73 (25)
    Dyslipidaemia: 20 (46) vs. 150 (51)

    Inclusion criteria: Assigned to T-TEER at the Medical University of Vienna and the Clinic for General and Interventional Cardiology/Angiology at the Heart & Diabetes Center NRW in Bad Oeynhausen (Germany) between September 2018 and December 2022.  Each procedure was approved according to current guidelines and careful risk stratification.

    Exclusion criteria: NA

    Decrease to TR ≤2, %: 76 vs. 78

    Complications and Post-Procedure Events, Primary vs. Secondary TR, n (%):
    Single leaflet device attachment: 1 (2) vs. 14 (5), p=0.70


    Device embolization or thrombosis: 0 vs. 0, p>0.99
    Major bleeding: 1 (2) vs. 5 (2), p>0.99
    Conversion to surgery: 0 vs. 0, p>0.99
    CIED implantation: 0 vs. 1 (0), p>0.99

    Note: Major bleeding defined according to the Bleeding Academic Research Consortium type 3a or higher.

    Propensity score matching was performed.  Propensity scores were calculated using a multivariable logistic regression model.  The matching procedure involved a 1:1 ratio, using nearest neighbor matching and a caliper width fixed at 0.05 standard deviations of the propensity score.  The propensity score model was adjusted, accounting for differences in sex, age, body surface area, and atrial fibrillation.

    Reference: Stolz et al., 2024

    Country: Germany

    Study Design: Registry study, multicenter

    Purpose: To apply the clinical TRILUMINATE inclusion and exclusion criteria to a real-world T-TEER patient group and evaluate symptomatic and survival outcome in TRILUMINATE-eligible and TRILUMINATE-ineligible patients.

    Funding Source: Several authors received compensation from Edwards Lifesciences.  One speaking honoria from Abbott and another received honoria from Innoventric.

    Qualityα: No formal quality assessment performed due to single-arms study design.

    Notes: Patients were from a real-world T-TEER patient registry.  Specifically, the study included patients from 5 large European heart valve centers (Munich, Leipzig, Bad Oeynhausen, and Hamburg, Germany, and Bern, Switzerland) who underwent T-TEER for significant symptomatic TR from 2016 to 2022.

    Intervention: T-TEER using either PASCAL device or the MitraClip/TriClip system

    Comparator: NA

    Length of follow-up, median (IQR), days: Follow-up occurred at 1 year.

    Patients (N): 962
    Eligibility upon application of TRILUMINATE inclusion/exclusion criteria, n (%):
    Eligible: 527 (54.8)
    Ineligible: 435 (45.2)

    Age, years, mean (SD): 78.3 (7.3)

    Age ≥ 65, n (%): NR

    Sex, female, n (%): 50.1

    Race, n (%): NR

    Diagnosis, n (%):
    TR etiology, %:
    Secondary: 84.4%
    TR severity, n (%):
    Moderate: 18 (1.9)
    Severe: 482 (50.3)
    Massive: 312 (32.5)
    Torrential: 147 (15.3)
    NYHA functional class ≥ III, n (%): 850 (89)

    Comorbidities, n (%):
    Atrial fibrillation/atrial flutter: 849 (88.3)
    Dyslipidemia: 437 (45.5)
    CAD: 442 (45.9)
    Arterial hypertension: 812 (84.5)
    Stroke: 118 (12.3)
    Diabetes: 250 (26.0)
    Peripheral artery disease: 107 (11.2) 56
    CABG: 137 (14.3)
    PCI: 202 (21.0)
    COPD: 192 (20.0)

    Inclusion criteria: Patients eligible for T-TEER with significant symptomatic TR who received treatment in one of five large European heart valve centers from 2016-2022.

    Exclusion criteria: NR

    Primary endpoint:
    1-year survival, Eligible vs. Ineligible, %:
    All patients: 84.7 vs. 74.9, log-rank P<0.001; HR 1.71 (1.27-2.30)
    Excluding patients without successful TR reduction: 86.9 vs. 78.3, P=0.003

    Secondary endpoints:
    1-year survival, Eligible vs. Ineligible, %:
    Free from heart failure hospitalization: 14 vs. 22, P<0.001
    Free from TV surgery, repeat intervention, and heart failure hospitalization: 72.9 vs. 58.0, P<0.001

    TR severity reduction:
    Length of follow-up, median (IQR), days: 362 (162-396), n=760

    TR severity reduction to ≤2, %:
    Eligible vs. Ineligible: 81.9 vs. 84.8, P=0.671
    PASCAL vs. TriClip/MitraClip: 76.6 vs. 70.7

    TR severity reduction to ≤1, Eligible vs. Ineligible, %: 46.5 vs. 46.1, P=0.902

    NYHA functional class:
    Length of follow-up, median (IQR), days: 364 (182-405), n=729

    At follow-up, Eligible vs. Ineligible, n (%):
    I: 52 (13.5) vs. 26 (7.5),
    II: 172 (44.6) vs. 58 (45.5),
    III: 146 (37.8) vs. 135 (38.9),
    IV: 16 (4.1) vs. 28 (8.1), P=0.019

    Improved at least 1 functional class, %: 56.3 vs. 53.3, P=0.430

    QoL as measured by the Minnesota Living With Heart Failure Questionnaire, Baseline vs. Follow-up (n=275), mean (SD):
    Eligible: 36.9 (16.6) vs. 28.2 (17.8), P<0.001
    Ineligible: 38.7 (18.7) vs. 31.7 (19.1), P<0.001
    (Authors indicate difference is “comparable” for both groups.)

    Functional capacity measured as 6MWT, Baseline vs. Follow-up (n=451), m, mean (SD):
    Eligible: 268 (114) vs. 311 (123), P<0.001
    Ineligible: 242 (118) vs. 264 (119), P<0.001
    (Authors indicate difference is “comparable” for both groups.)

    NR

    Reference: Kodali et al., 2023

    Country: US

    Study Design: Single-arm, multicenter, non-randomized interventional study (CLASP TR EFS NCT03745313)

    Purpose: To evaluate the 1-year outcomes of the PASCAL transcatheter valve repair system (Edwards Lifesciences) to treat TR.

    Funding Source: Edwards Lifesciences

    Qualityα: No formal quality assessment performed due to single-arms study design.

    Notes: The study was overseen by an independent clinical events committee that adjudicated MAEs through 1 year.

    Intervention: Transcatheter tricuspid valve repair with PASCAL

    Comparator: NA

    Length of follow-up, days, median (IQR): 590 (742)
    Note: Patients are followed up at discharge, at 30 days, at 6 months, at 1 year, and annually for 5 years post-implantation.

    Patients (N): 65

    Age, years, mean (SD): 77.4 (8.9)

    Age ≥ 65, n (%): NR

    Sex, female, n (%): 36 (55.4)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA functional class III or IV: 46 (70.8)
    TR severe or greater: 62 (97.0)

    Comorbidities, n (%):
    Atrial fibrillation/flutter: 58 (89.2)
    CAD: 19 (29.2)
    Pulmonary hypertension: 34 (53.1)
    Myocardial infarction: 4 (6.2)
    Stroke: 7 (10.8)
    Transient ischemic attack: 6 (9.2)
    Conduction defects/heart block: 23 (35.4)
    Renal insufficiency or failure: 28 (43.1)
    Diabetes: 10 (15.4)
    Ascites: 18 (27.7)
    COPD: 11 (16.9)
    Gastrointestinal or esophageal bleeding:
    5 (7.7)
    Cirrhosis: 6 (9.2)

    Inclusion criteria: Symptomatic, severe functional or degenerative TR, symptoms despite medical therapy, and deemed suitable for the procedure by their local heart team.

    Exclusion criteria: Unsuitable TR anatomy, as assessed by echocardiography; previous TV repair or replacement; severe chronic kidney disease, with estimated glomerular filtration rate #30 mL/ min/1.73 m2 or requiring long-term dialysis; hemodynamic instability or intravenous inotropic therapy unless part of prehabilitation; and significant frailty (ie, Katz Index of Independence in Activities of Daily Living #2) within 3 months of the scheduled procedure

    Endpoints:
    Implant success, n (%): 59 (91)
    Note: Success defined as implant deployment and implant catheter retrieved as intended.

    Procedural success, n (%): 49 (88)
    Note: Success defined as implant success with at least 1 TR grade reduction at the end of the procedure on intraprocedural TEE as assessed by the core laboratory without the need for surgical or percutaneous intervention before hospital discharge.

    Clinical success, n (%): 43 (77)
    Note: Success defined as procedural success without MAEs at 30 days.

    NYHA functional class of I or II:
    30 days: 88%; vs. baseline, P<0.001
    1 year: 92%; vs. 30 days, P=0.395

    QoL, as assessed using the Kansas City Cardiomyopathy Questionnaire, mean (SD):
    Baseline: 53 (20)
    30 days: 71 (22); vs. baseline, P<0.001
    1 year: 72 (23), vs. 30 days, p=0.854

    Functional endpoint: 6MWT, m, mean (SD):
    Baseline: 208 (107)
    30 days: 270 (152); vs. baseline, P<0.001
    1 year: 311 (218); vs. 30 days, P=0.068

    Composite of MAEs at 30 days and 1 year, n (%): 6 (9.2); 11 (16.9)
    Note: MAEs included cardiovascular mortality, myocardial infarction, stroke, renal complications requiring unplanned dialysis or renal replacement therapy, unplanned or emergency reintervention (either percutaneous or surgical) related to the device, severe bleeding as defined by the Mitral Valve Academic Research Consortium, and major access site and vascular complications requiring intervention.

    MAEs, 30 days and 1 year, n (%):
    Cardiovascular mortality: 2 (3.1); 5 (7.7)
    Myocardial infarction: 0 (0.0); 0 (0.0)
    Stroke: 1 (1.5); 3 (4.6)
    Renal complications requiring unplanned dialysis or renal replacement therapy: 0 (0.0); 0 (0.0)
    Severe bleeding: 5 (7.7); 6 (9.2)
    Unplanned or emergency reintervention related to the device: 0 (0.0); 1 (1.5)
    Major access site and vascular complications requiring intervention: 2 (3.1); 2 (3.1)

    Other events, 30 days and 1 year, n (%):
    All-cause mortality: 2 (3.1); 7 (10.8)
    Heart failure hospitalization: 0 (0.0); 12 (18.5)
    Single-leaflet device attachment: 3 (4.6); 3 (4.6)

    Reference: Wild et al., 2025

    Country: Germany, Sweden, Switzerland

    Study Design: Multicenter, observational cohort study across 16 European heart valve centers

    Purpose: To investigate the safety and effectiveness of the PASCAL transcatheter valve repair system for treating severe tricuspid regurgitation (TR) in a real-world patient population

    Funding Source: NR

    Qualitya: No formal quality assessment performed due to single-arms study design.

    Notes: NA

    Intervention: Transcatheter tricuspid valve repair with PASCAL

    Comparator: NA

    Length of follow-up, days, median (IQR): 1 year

    Patients (N): 1,059

    Age, years, mean (SD): 79 (9)

    Age ≥ 65, n (%): NR

    Sex, female, %: 53

    Race, n (%): NR

    Diagnosis, %:
    NYHA functional class III or IV: 87
    TR severe or greater: 96

    Comorbidities, %:
    Atrial fibrillation/: 91
    Chronic kidney disease: 79
    CIED: 27
    PH: 66
    HFrEF Advanced: 16
    Edema: 66
    Ascites: 15

    Inclusion criteria: Patients in the PASTE treated with the PASCAL transcatheter valve repair system from February 2019 to November 2023.

    Exclusion criteria: NR

    Endpoints:
    Implant success, %: 98

    Acute procedural success, %: 95

    TR reduced to moderate or less, %: 87

    TR reduced to mild or less, %: 55

    TR sustained at moderate or less, %: 83

    NYHA functional class of I or II:
    66% improved to class I/II at 1 year

    Clinical success rate, %: 53
    Note: Defined as survival without significant TR recurrence or HFH, as well as symptomatic improvement.

    30 day mortality, %: 1.3

    30 day HFH, %: 1.6

    Reference: Hanses et al., 2023

    Country: Germany

    Study Design: Single-arm interventional study with subgroup analysis

    Purpose: To evaluate the impact of RVCPi on outcome in patients with severe TR who underwent T-TEER.

    Funding Source: None

    Qualityα: No formal quality assessment performed due to single-arm study design

    Notes: NA

    Intervention: T-TEER with TriClip or PASCAL

    Comparator: NA

    Length of follow-up, mean: Follow-up occurred at baseline, 30 days, and 1 year

    Patients (N): 102
    High RVCPi: 32
    Low RVCPi: 70

    Age, years, mean (SD): 81 (6)

    Age ≥ 65, n (%): NR

    Sex, female, n (%): 52 (51)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA class:
    II: 5 (5)
    III: 73 (72)
    IV: 24 (24)
    TR severity:
    Severe: 41 (40)
    Massive: 39 (38)
    Torrential: 22 (22)

    Comorbidities, n (%):
    CAD: 45 (44)
    Hypertension: 73 (72)
    Previous cardiovascular procedures: 58 (57)
    Percutaneous coronary intervention: 9 (9)
    Coronary artery bypass graft: 12 (12)
    Mitral valve – TEER: 20 (20)
    Heart rhythm:
    Atrial fibrillation: 85 (83)
    Pacemaker: 7 (7)
    Sinus rhythm: 10 (10)
    Diabetes: 22 (22)
    Peripheral artery disease: 7 (7)
    COPD: 13 (13)

    Inclusion criteria: Patients with severe TR who underwent T-TEER from August 2020 to March 2022.

    Exclusion criteria: NA

    30-day post-T-TEER, High RVCPi vs. Low RVCPi, %:
    All-cause mortality: 12 vs. 7, p=0.5
    Rehospitalization of patients with CHD: 9 vs. 1, p=0.09

    Primary endpoint:
    1-year all-cause mortality and heart failure hospitalization, High RVCPi vs. Low RVCPi, n (%): 17 (53) vs. 13 (21), log-rank p<0.001

    Multivariate Cox proportional-HR analysis, HR (95% CI):
    RVCPi: 2.64 (1.38, 5.05), p=0.003
    Age: 0.94 (0.87, 1.00), p=0.064
    Male (female ref): 1.26 (0.51, 3.16), p=0.6
    COPD: 1.10 (0.35, 3.48), p=0.9
    TAPSE/PASP (mm/mmHg): 0.26 (0.04, 1.86), p=0.2
    Failed clip: 14.5 (1.91, 110), p=0.010
    NT-proBNP (ng/1): 3.22 (1.75, 5.92), p<0.001

    Secondary endpoint:
    1-year all-cause mortality, High RVCPi vs. Low RVCPi, n (%):
    12 (38) vs. 11 (18), log-rank p<0.024
    1-year all-cause mortality, n (%): 23 (25)

    Other endpoints:
    TR severity ≤ 2 at was high and similar in both groups High RVCPi vs. Low RVCPi, %: 68 vs. 75.9 (based on graph)

    1-year hospitalized for CHD, n (%): 12 (13)

    In-hospital MAEs, High RVCPi vs. Low RVCPi, n (%):
    Death: 1 (3) vs 2 (3), p>0.9
    Pericardial tamponade: 0 (0) vs. 0 (0)
    Transfusion (≥2 Units of blood): 3 (9) vs. 5 (7), p=0.7
    Myocardial infarction: 0 (0) vs. 0 (0)
    Major stroke: 0 (0) vs. 0 (0)
    Acute thrombosis: 0 (0) vs. 0 (0)
    Acute dialysis: 0 (0) vs. 0 (0)
    Failed procedure: 2 (6) vs. 2 (3), p=0.6
    Mechanical ventilation > 48 hours: 0 (0) vs. 1 (1), p>0.9

    Reference: Patrascu et al., 2022

    Country: Germany

    Study Design: Prospective, single-center, single-arm, registry Pforzheim
    Tricuspid Valve Registry (NCT05179616)

    Purpose: To test the hypothesis that percutaneous therapy with the TriClip system is safe and effective in symptomatic, high-grade TR patients at high and prohibitive risk and that procedural success is the main determinant of short-term outcome, regardless of expected morbidity and mortality

    Funding Source: None

    Qualityα: NA

    No formal quality assessment performed due to single-arm study design.

    Notes: Echocardiographs were assessed independently by cardiac imaging specialists blinded to procedural details. 29/33 patients reached 6 months of follow-up.

    Intervention: T-TEER with TriClip

    Comparator: NA

    Length of follow-up, mean: NR; patients followed for 6 months

    Patients (N): 33
    Prohibitive risk: 18
    High risk: 15

    Age, years, mean (SD): 81.9 (5.1)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 17 (51.5)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA Functional Class
    I or II: 5 (15)
    III or IV: 28 (85)
    TR etiology:
    Functional, associated with annular dilation, leaflet tethering, or both: 33 (100)
    TR grade:
    Severe: 7 (21)
    Massive or torrential: 26 (79)

    Comorbidities, n (%):
    Atrial fibrillation: 32 (97.0)
    Pulmonary hypertension: 33 (100)
    COPD: 8 (24.2)
    Chronic kidney disease stage 3-5: 26 (78.8)
    Previous stroke/TIA: 6 (18.2)
    CAD: 18 (54.5)
    Pacemaker/ICD/CRT: 7 (21.2)
    Previous percutaneous mitral valve intervention: 9 (27.3)
    Previous surgical mitral valve intervention: 2 (6.1)

    Inclusion criteria: Symptomatic high-grade TR; assessed as eligible by the Heart Team; ineligible for conventional therapy

    Exclusion criteria: Treatable left heart disease (e.g., high-grade mitral regurgitation); sPAP>70mmHg; age <18 years; primary TR; cardiac implantable device-related TR

    Note: This study examined T-TEER outcomes in prohibitive risk vs. high risk patients; thus, the paper presents patient characteristics and outcomes data separately for each group.  Abstracted data combines both groups’ data where possible, since we are treating this as a single-arm study.  If it is not possible to aggregate the data, then the separated data is abstracted.

    Primary endpoint:
    TR reduction ≥1 grade (procedural success), at 30 days, n (%):
    31 (93.9)

    TR grade, 30 days vs. 6 months, n (%):
    Trivial: 10 (30) vs. 8 (28)
    Moderate: 8 (24) vs. 10 (34)
    Severe: 12 (37) vs. 7 (24)
    Massive: 3 (9) vs. 4 (14)
    Torrential: 0 (0) vs. 0 (0)

    TR reduction ≥2 grades, at 6 months, n (%):
    18 (62)

    Secondary endpoints:
    Device success (placement of ≥1 clip): 33 (100)

    Functional capacity, NYHA Class, at 6 months, n (%):
    I or II: 24 (83)
    III or IV: 5 (17)

    Note: Within-group reductions of III or IV patients were statistically significant.

    QoL, KCCQ, BL vs. 6 months, mean (SD) points:
    Prohibitive risk: 25.4 (16.7) vs. 50.5 (20.3)
    Difference: 25.1 (16.7), p<0.001***, favoring 6 months
    High risk: 34.7 (18.3) vs. 60.6 (18.8)
    Difference: 25.9 (12.1), p<0.001***, favoring 6 months

    Exercise capacity, 6MWT, BL vs. 6 months, mean (SD) meters:
    Prohibitive risk: 144 (92.6) vs. 225 (124.1)
    Difference: 85.8 (47.9), p<0.001***, favoring 6 months
    High risk: 205.6 (100) vs. 291.4 (103)
    Difference: 81 (43.6), p<0.001***, favoring 6 months

    Functional and morphologic parameters, BL vs. 6 months, mean (SD) or % (n/N):
    Format: Prohibitive risk; High risk
    TR parameters:
    PISA EROA, mm2: 87.2 (35.2) vs. 36.7 (22.9), p<0.001*** ; 71.8 (24.1) vs. 14.1 (15), p<0.001***
    Mean vena contracta, mm: 18.3 (3.8) vs. 9.1 (4), p<0.001*** ; 14.2 (4.3) vs. 5.5 (3.8), p<0.001***
    TR volume, mL/beat: 88.7 (34.5) vs. 37.2 (25.5), p<0.001*** ; 71.2 (28.8) vs. 14.9 (18.8), p<0.001***
    PISA, mm: 9.6 (2.6) vs. 6.4 (3.2), p<0.001*** ; 8.8 (1.5) vs. 4.1 (2.5), p<0.001***
    Jet area (4-ch), cm2: 18.9 (6.5) vs. 11.5 (6.4), p<0.001*** ; 15.7 (7.9) vs. 9.2 (9.7), p<0.001***
    IVC diameter, mm: 25.6 (6.2) vs. 17 (6.5), p<0.001*** ; 24.5 (5.9) vs. 14.1 (3.5), p<0.001*** Hepatic vein flow reversal: 88.9 (16/18) vs. 20 (3/15), p=0.001** ; 60 (9/15) vs. 7 (1/14), p=0.004**
    Right heart remodeling:
    RA indexed volume, mL/m2: 99.5 (38.9) vs. 56.3 (42.6), p=0.005** ; 86 (63.4) vs. 61 (59.1), p=0.002**
    Base RVEDD (4-ch), mm: 54.7 (8.3) vs. 48.8 (6.8), p<0.001*** ; 57.6 (8.5) vs. 49.2 (7.5), p<0.001***
    TV annular diameter, mm: 47 (8.2) vs. 42.1 (7.1), p=0.001** ; 44.6 (6.2) vs. 40.4 (6.5), p<0.001***
    Ventricular systolic function:
    RV TAPSE, mm: 14.2 (3.1) vs. 17.7 (2.2), p<0.001*** ; 16.4 (3.5) vs. 20.7 (5.4), p<0.001*** RV FAC, %: 30 (8.1) vs. 37.7 (9.7), p<0.001*** ; 30.4 (8.3) vs. 40.1 (8.5), p<0.001***
    Annular velocity TDI, cm/s: 9.9 (2.3) vs. 11.9 (8.2), p<0.001*** ; 9.9 (2.6) vs. 11.4 (2.9), p=0.003** LVEF, %: 49.4 (4.2) vs. 50.5 (10.7), p=0.001** ; 58.2 (6.6) vs. 59.1 (5.9), p<0.001***
    Hemodynamic parameters:
    TR peak velocity, cm/s: 323.3 (41.5) vs. 289.2 (40.5), p=0.001** ; 324.7 (36.5) vs. 279.7 (52.4), p<0.001***
    PAPs, mmHg: 60.9 (12) vs. 48.1 (11.5), p<0.001*** ; 59.8 (14.1) vs. 44.7 (15.1), p<0.001***
    LV stroke volume, mL: 51.3 (9.4) vs. 57.1 (8.9), p<0.001*** ; 56.6 (9) vs. 58.2 (11.8), p=0.629 Cardiac output, L/min: 3.6 (0.7) vs. 4 (0.6), p<0.001*** ; 4.0 (1.1) vs. 4.2 (0.9), p=0.442
    RV stroke volume, mL: 59.6 (11.5) vs. 63.2 (11.1), p<0.001*** ; 59.7 (9.5) vs. 63.2 (11.7), p=0.033*

    Oral diuretic dose reduction, at discharge:
    Prohibitive risk: 27%
    High risk: 33%

    Change in renal and hepatic function parameters, BL to 6 months, mean (SD):
    Format: Prohibitive risk ; High risk
    GFR, mL/m2/1.73m2: 6.2 (8.4), p=0.048* ; 6.1 (12.3), p=0.05
    AST, U/L: -6 (9.9), p=0.02* ; -9.8 (8.2), p=0.052
    NTproBNP, pg/mL: -2077.1 (2064.8), p=0.002** ; -168 (2009.1), p=0.849

    Primary endpoint:
    Composite MAEs, at 6 months: 18.1%

    Safety events, at 6 months, n (%):
    CV mortality: 3 (9)
    All-cause mortality: 4 (12) 
    Device-related AEs: 0 (0)
    MI: 0 (0)
    Major bleeding: 2 (6)
    Vascular complications: 1 (3)
    Emergency cardiac surgery: 0 (0)
    New-onset renal failure: 0 (0)
    New-onset liver failure: 0 (0)
    TV stenosis: 0 (0)
    Stroke: 0 (0)
    Rehospitalization for acute HF: 6 (18)
    Noncardiac rehospitalization: 6 (18)

    Retrospective Studies

    Reference: Alachkar et al., 2023

    Country: Germany, Switzerland

    Study Design: Single-arm interventional study with subgroup analysis

    Purpose: To evaluate the feasibility and efficacy of t-TEER in patients with CIED

    Funding Source: None

    Qualityα: No formal quality assessment performed due single-arm study design.

    Notes: NA

    Intervention: t-TEER with TriClip or PASCAL

    Comparator: NA

    Length of follow-up: Post-procedure

    Patients (N): 106
    Non-CIED: 81
    CIED: 25

    Age, years, mean (SD): 80.1 (6.4)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 64 (60.4)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA Class, n (%):
    I: 1
    II: 23
    III: 65
    IV: 6
    Severity of TR, TEER vs. MT, n (%):
    III: 60 (56.6) (Severe)
    IV: 42 (39.6) (Massive)
    V: 4 (3.8) (Torrential)

    Comorbidities, n (%):
    Diabetes: 29 (27.3)
    Hypertension: 88 (83)
    Atrial fibrillation: 94 (88.6)
    Chronic renal failure: 83 (78.3)
    Dialysis: 4 (0.4)
    Peripheral artery disease: 9 (8.4)
    COPD: 17 (16)
    CAD: 60 (42.1)
    Previous PCI: 92 (86.7)
    Previous CABG: 11 (10.3)
    Previous other cardiac surgery: 10 (9.4)
    Previous mitral valve TEER: 26 (24.5)
    Previous aortic valve intervention: 3 (2.8)

    Inclusion criteria: All patients had symptomatic severe TR as defined by the guidelines of the European Society of Cardiology.  All patients were evaluated by the heart team, which included an interventional cardiologist, a cardiac surgeon, and an anesthetist, and were deemed to be non-operable.  Patients with TR caused mainly by the CIED lead such as lead impinging one of the leaflets were deemed not appropriate for TEER.  In all included cases, the multidisciplinary heart team recommended proceeding with t-TEER.

    Exclusion criteria: NR

    Success of the procedure, Non-CIED vs. CIED, n (%): 76 (93.8) vs. 23 (92), p=0.748
    Note: Success was defined as implantation of 1 or more clips and a reduction in TR of at least 1 grade.

    Duration of the procedure, Non-CIED vs. CIED, minutes, mean (SD): 92.1 (37.9) vs. 83.4 (30.1), p=0.324

    TR severity, non-CIED vs. CIED, n (%):
    I: 37 (45.7) vs. 10 (40),
    II: 37 (45.7) vs. 13 (52),
    III: 3 (3.7) vs. 1 (4),
    IV: 3 (3.7) vs. 1 (4),
    V: 1 (1.2) vs. 0 (0), p = 0.961

    Pressure gradient across the tricuspid valve, non-CIED vs. CIED, mmHG, mean (SD): 2.8 (1.2) vs. 2.9 (1.2), p=0.811

    Vascular complications, Non-CIED vs. CIED, n (%): 7 (8.6) vs. 3 (12), p=0.616

    Intrahospital mortality, n (%): 9 (8.4)
    Non-CIED vs. CIED: 8 (9.9) vs. 1 (4), p=0.357

    Reference: Mattig et al., 2023

    Country: Germany

    Study Design: Non-randomized interventional study

    Purpose: To provide a comparison of procedural characteristics and learning curves of the most widely used TR devices, i.e., percutaneous annuloplasty and T-TEER, in a real-world cohort.

    Funding Source: Abbott

    Qualityα: Poor; the initial groups differed for the presence of CIEDs, bilirubin levels, and peripheral artery disease.  There was also a lack of concealment and adjustment for confounders.

    Notes: The authors indicate that this is a retrospective study of a real-world cohort of patients who underwent one of the two procedures in two centers between 2019 and 2022.  However, it reads as though this is an interventional study.

    Intervention: T-TEER with TriClip or PASCAL

    Comparator: Percutaneous annuloplasty with Cardioband implantation

    Length of follow-up: Post-procedure

    Patients (N): 122
    Intervention: 58
    Comparator: 64

    Age, years, Intervention vs. Comparator, median (IQR):
    82 (79–84) vs. 81 (77–84)

    Age ≥ 65, n (%): NA

    Sex, female, Intervention vs. Comparator, n (%): 33 (57) vs. 41 (64)

    Race, n (%): NR

    Diagnosis, Intervention vs. Comparator, n (%):
    NYHA class:
    I: 0 (0) vs. 0 (0)
    II: 11 (19) vs. 13 (20)
    III: 42 (72) vs. 47 (75)
    IV: 5 (9) vs. 4 (6)
    TR severity:
    Severe to torrential: 100%

    Comorbidities, Intervention vs. Comparator, n (%):
    CAD: 32 (55) vs. 36 (56)
    PCI: 22 (38) vs. 20 (31)
    CABG: 6 (10) vs. 2 (3)
    CIED: 25 (43) vs. 13 (20)
    Atrial fibrillation: 53 (91) vs. 62 (97)
    Arterial hypertension: 47 (81) vs. 55 (86)
    Diabetes: 16 (28) vs. 17 (27)
    Stroke: 9 (16) vs. 11 (17)
    PAD: 12 (21) vs. 5 (8)
    COPD: 12 (21) vs. 10 (16)
    Asthma: 3 (5) vs. 2 (3)

    Inclusion criteria: Age ≥18 years, high surgical risk, and symptomatic severe to torrential TR of different pathologies and despite optimal MT

    Exclusion criteria: Patients with combined procedures of the tricuspid and mitral valve.

    TR grade ≤2 post-intervention, Intervention vs. Comparator, %: 91 vs. 100

    TR reduction, Intervention vs. Comparator, mean (SD): 2.4 (0.8) vs. 2.5 (0.8)

    Technical and device success, Intervention vs. Comparator, %: 97 vs. 98

    Decrease in TA diameter significant for both Intervention and Comparator
    Note: Graph results only presented.

    Echocardiographic characteristics, Baseline vs. Discharge:
    RV fractional area change, mean (SD), n:

    Intervention: 41 (11) vs. 36 (9), n=43, p=0.003
    Comparator: 39 (7) vs. 35 (9), n=43, p=0.004
    Intervention vs. Comparator at Discharge, p=0.699
    Left ventricular ejection fraction, % (IQR), n:
    Intervention: 51 (45–55) vs. 55 (52–59), n = 56, p<0.001
    Comparator: 55 (50–59) vs. 55 (50–60), p=0.361
    Intervention vs. Comparator at Discharge, p=0.827
    RV diameter basal, mm (SD), n:
    Intervention: 49 (10) vs. 46 (10), n=56, p=0.008
    Comparator: 47 (9) vs. 45 (9), n=53, p=0.159
    Intervention vs. Comparator at Discharge, p=0.838
    RV diameter mid, mm (SD), n:
    Intervention: 38 (10) vs. 36 (10), n=52, p=0.107
    Comparator: 37 (9) vs. 37 (9), n=50, p=0.659 Intervention vs. Comparator at Discharge, p=0.383
    RA area, cm2, (IQR):
    Intervention: 34 (28–43) vs. 33 (27–40), p=0.007
    Comparator: 33 (29–40) vs. 29 (25–35), p<0.001 Intervention vs. Comparator at Discharge, p<0.001
    TAPSE, mm (SD), n:
    Intervention: 17 (4) vs. 17 (4), n=51, p=0.765 Comparator: 19 (5) vs. 15 (4), n=58, p<0.001
    Intervention vs. Comparator at Discharge, p<0.002

    Procedure time, Intervention vs. Comparator, median minutes: 102 (73-122) vs. 165 (143-236), p<0.001

    Procedural complications, Intervention vs. Comparator, n (%):
    Injury of the right coronary artery requiring intervention: 0 (0) vs. 3 (5), p=0.092
    Transient bradycardia: 0 (0) vs. 4 (6), p=0.051
    Single leaflet device attachments: 4 (7) vs. 0 (0), p= 0.034
    Pericardial effusion: 3 (5) vs. 17 (27), p= 0.001
    Access complication: 0 (0) vs. 1 (2), p=0.335

    Reference: Freixa et al., 2022

    Country: Spain

    Study Design: Multi-center (4 sites), single-arm, retrospective cohort

    Purpose: To describe the initial experience with T-TEER using TriClip in Spain between Jun 2020 and Mar 2021

    Funding Source: None; XF, LS, DA, RE-L, and MS have served as proctors for Abbott

    Qualityα: NA
    No formal quality assessment performed due to single-arm study design.

    Notes: Data for all patients available at 3 months.  No independent adjudication of clinical events done or involvement of core lab for echo analysis.

    Intervention: T-TEER with TriClip

    Note: One patient underwent concomitant transcatheter mitral valve repair. TriClip G4 not used.

    Comparator: NA

    Length of follow-up, mean: NR
    Note: Patients were followed for 3 months.

    Patients (N): 34

    Age, years, median (IQR): 75.5 (69-79)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 25 (74)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA Functional Class:
    I: 0 (0)
    II: 8 (24)
    III: 22 (67)
    IV: 3 (9)
    TR severity:
    None to moderate: 0 (0)
    Severe: 16 (47)
    Massive: 15 (44)
    Torrential: 3 (9)
    TR etiology:
    Functional: 27 (79)
    Degenerative: 1 (3)
    Mixed: 6 (18)
    Lead-induced: 1 (3)
    Mitral regurgitation severity:
    No: 8 (24)
    Mild: 20 (61)
    Moderate: 3 (9)
    Moderate-severe: 1 (3)
    Severe: 1 (3)

    Comorbidities, n (%):
    BMI, mean (SD): 26.8 (4.86)
    Hypertension: 19 (56)
    Pulmonary hypertension: 0 (0)
    Diabetes mellitus: 7 (20)
    Atrial fibrillation: 31 (91)
    COPD: 5 (15)
    CAD: 2 (6)
    Stroke/TIA: 6 (18)
    Chronic kidney disease: 14 (41)
    PPM/ICD lead: 1 (3)
    Previous mitral valve surgery: 9 (27)
    Previous TV surgery: 1 (3)
    Previous MitraClip: 2 (6)

    Inclusion criteria: NR

    Exclusion criteria: NR

    Note: Patients were evaluated by a team of interventional cardiologists, HF specialists, expert imaging, cardiologists, and heart surgeons.

    Primary endpoint:
    TR reduction ≥1 grade, at discharge, n (%):
    34 (100)

    Other endpoints:
    Residual TR severity ≤ moderate, n (%):
    Post-procedural: 33 (97)
    At discharge: 31 (91)
    Patients w/ coaptation gap <7mm: 24/26 (92)
    Patients w/ coaptation gap 7-10mm: 7/8 (88)
    At 3 months: 25 (80), p<0.001*** compared to BL, favoring 3 months

    NYHA Class, at 3 months, n (%):
    ≤ Class II: 28 (88), p<0.001*** compared to BL, favoring 3 months
    Class III: 3 (10)
    Class IV: 1 (3)

    Change in diuretic dose, at 3 months, n (%):
    None: 13 (41)
    Reduced: 17 (53)
    Increased: 2 (6)

    Furosemide dose, BL vs. 3 months, mean (SD) mg/day: 60 (7.23) vs. 45 (7.5), p<0.05*, favoring 3 months

    Echocardiographic parameters, BL vs. 3 months:
    Right atrium area, median (IQR) cm2 :
    28 (22.7-35) vs. 28.1 (22-36)
    Difference: -0.7 (-6-4), p=0.31
    RV end-diastolic area, median (IQR) cm2:
    21.6 (19-28) vs. 18.8 (16.8-24.8)
    Difference: -2.1 (-4.9-0), p=0.021*, favoring 3 months
    RV FAC, median (IQR):
    40 (35-47) vs. 38.5 (33-47)
    Difference: 0 (-8-6), p=0.818
    TAPSE, median (IQR) cm:
    18 (15-20) vs. 1.8 (1.4-1.9)
    Difference: -0.3 (-6-0.5), p=0.10
    Vena contracta, median (IQR) cm:
    1.32 (0.9-12) vs. 0.6 (0.3-0.9)
    Difference: -0.6 (-0.87-(-0.27)), p=0.018*, favoring 3 months
    IVC collapse >50%, mean n (SD): NR vs. 13 (54)
    IVC max diameter, median (IQR) mm:
    23 (20-27) vs. 18 (16-23)
    Difference: -4 (-5.5-(-1)), p=0.013*, favoring 3 months

    MAEs, n (%):
    Post-procedure:
    Mortality: 0 (0)
    Cardiac tamponade: 0 (0)
    Emergent surgery: 0 (0)
    Vascular complications: 0 (0)
    Major bleeding: 0 (0)
    Stroke: 0 (0)
    MI: 0 (0)

    At 3 months:
    Mortality: 0 (0)
    CV mortality: 0 (0)
    Admissions for HF: 3 (10)

    Technical complications, n (%):
    Procedural:
    Partial detachment: 1 (3)
    Total detachment: 0 (0)
    Leaflet perforation: 0 (0)
    Chordae rupture: 0 (0)
    At 3 months:
    Partial detachment: 0 (0)
    Total detachment: 0 (0)

    Reference: Haurand et al., 2022

    Country: Germany

    Study Design: Multi-center (3 sites), single-arm, retrospective cohort

    Purpose: To investigate whether T-TEER can be performed effectively and safely using deep sedation and without general anesthesia in highly experienced centers

    Funding Source: NR

    GN and SB have received research grants and speaker honoraria from Abbott.

    Qualityα: NA

    No formal quality assessment performed due to single-arm study design.

    Notes: Central analysis based on anonymized data.  Highly experienced care centers included in study.

    Intervention: T-TEER with TriClip

    Comparator: NA

    Length of follow-up, mean: NR
    Note: Patients were followed to discharge, with the IQR of hospital stay as 5-11 (median 6 days for deep sedation and 8 days for general anesthesia).

    Patients (N): 104
    Deep sedation: 40
    General anesthesia: 64

    Age, years, range: 76-84
    Age ≥ 65, n (%): 104 (100)

    Sex, female, n (%): 58 (55.8)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA Functional Class:
    II: 20 (19.2)
    III: 73 (70.2)
    IV: 11 (10.6)
    TR severity:
    Moderate: 3 (2.9)
    Severe (includes massive and torrential): 101 (97.1)

    Comorbidities, n (%):
    Atrial hypertension: 68 (65.4)
    Diabetes mellitus: 20 (19.2)
    Previous MI: 16 (15.4)
    Previous cardiac bypass surgery: 13 (12.5)
    Previous mitral valve surgery: 12 (11.5)
    Pacemaker/ICD/CRT: 22 (21.2)
    Atrial fibrillation: 92 (88.5)
    Chronic lung disease: 19 (18.3)
    Previous stroke: 10 (9.6)

    Inclusion criteria: Significant TR; treated with TriClip between Sep 2020 and Sep 2021

    Exclusion criteria: NR

    Note: This study examined T-TEER outcomes in deep sedation vs. general anesthesia patients; thus, the paper presents patient characteristics and outcomes data separately for each group.  Abstracted data combines both groups’ data where possible, since we are treating this as a single-arm study.

    Primary endpoints:
    Technical success (implantation of ≥1 device and reduction of TR ≥1 degree), at discharge, n (%):
    97 (93.3)

    Severity of TR, BL vs. at discharge, n (%):
    Mild: 0 (0) vs. 33 (32.4)
    Moderate: 0 (0) vs. 44 (43.1)
    Severe: 56 (53.8) vs. 21 (20.6)
    Massive: 29 (27.9) vs. 2 (2.0)
    Torrential: 19 (18.3) vs. 2 (2.0)

    Composite endpoint of in-hospital complications, n (%): 5 (4.8)
    All-cause mortality: 2 (1.9)
    Conversion to surgery: 0 (0)
    MI: 0 (0)
    Stroke: 0 (0)
    Pneumonia: 3 (2.9)
    Major or life-threatening bleeding: 0 (0)
    Periprocedural conversion to general anesthesia: 0 (0)

    Other safety endpoints, procedurally:
    Early SLDA: 3 (2.9)
    Leaflet laceration: 1 (1.0)
    Acute renal failure: 9 (8.6)
    Minor bleeding: 10 (9.6)

    Reference: Hellhammer et al., 2022

    Country: Germany

    Study Design: Single-center, single-arm, retrospective cohort

    Purpose: To determine TEE complications during T-TEER

    Funding Source: NR

    Qualityα: NA
    No formal quality assessment was performed due to single-arm study design.

    Intervention: T-TEER with TriClip

    Comparator: NA

    Length of follow-up, mean: NR; patients were followed procedurally

    Patients (N): 64

    Age, years, mean (SD): 80 (6.2)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 38 (59.4)

    Race, n (%): NR

    Diagnosis: TR (no other details provided)

    Comorbidities, n (%):
    CAD: 34 (53.1)
    Previous heart surgery: 16 (25.0)
    Atrial fibrillation: 57 (89.1)
    Peripheral artery vascular disease: 5 (7.8)
    Cerebrovascular artery disease: 7 (10.9)
    Obstructive sleep apnea syndrome: 3 (4.7)
    COPD: 5 (7.8)
    Diabetes mellitus: 13 (20.3)
    Dialysis: 0 (0)
    Anemia: 23 (35.9)

    Inclusion criteria: All patients referred to T-TEER procedure using TriClip between Apr 2019 and Jun 2021

    Exclusion criteria: None defined

    Reduction in TR severity, grades, mean (SD):
    2.1 (0.8)

    Procedural success (implantation of ≥1 clip with TR reduction ≥1 grade), n (%): 57 (91.9)

    TEE-related complications, n (%):
    Overall: 2 (3.1)
    Major complications: 1 (1.6)
     Perforation of esophageal mucosa leading to upper GI bleeding: 1 (1.6)
    Minor complications: 1 (1.6)
     Hematemesis: 1 (1.6)

    In-hospital mortality, n (%): 0 (0)

    Note: Major complications met one of the following criteria: (1) upper GI bleeding requiring inotropes or blood transfusion, (2) mechanical lesions as perforations of esophagus or stomach requiring endoscopic or surgical intervention, and (3) persistent dysphagia requiring further diagnostic.  Minor TEE related complications were considered as dysphagia or perioral hypesthesia persisting within 24 hours after procedure, hematemesis without need for blood transfusion.

    Reference: Sugiura et al., 2021

    Country: Germany

    Study Design: Single-center, single-arm, retrospective cohort

    Purpose: To assess the anatomical leaflet variation and investigate its impact on the procedural outcome in patients undergoing T-TEER

    Funding Source: NR

    Qualityα: NA
    No formal quality assessment was performed due to single-arm study design.

    Intervention: T-TEER with TriClip, MitraClip, or PASCAL

    Comparator: NA

    Length of follow-up, median (IQR): 8 months (4-16)

    Patients (N): 145
    TriClip: 17 (11.7%)
    MitraClip: 104 (71.7%)
    PASCAL: 24 (16.6%)

    Age, years, mean (SD): 78 (8)
    Age ≥ 65, n (%): NR

    Sex, female, n (%): 80 (55.2)

    Race, n (%): NR

    Diagnosis, n (%):
    NYHA Functional Class:
    II: 19 (13.1)
    III: 98 (67.6)
    IV: 28 (19.3)
    TR severity:
    Severe: 69 (47.6)
    Massive: 41 (28.3)
    Torrential: 35 (24.1)
    TR etiology:
    Functional: 134 (92.4)
    Mitral regurgitation grade ≥moderate: 21 (14.5)

    Comorbidities, n (%):
    Hypertension: 128 (87.1)
    COPD: 36 (24.8)
    CAD: 85 (58.6)
    Prior MI: 39 (26.9)
    Atrial fibrillation: 137 (93.8)

    Inclusion criteria: Symptomatic TR; underwent T-TEER with MitraClip, TriClip, or PASCAL systems from Jun 2015 to Jul 2020; deemed as ineligible or at high risk for conventional surgery

    Exclusion criteria: NR

    Note: Enrolled patients received either TriClip, MitraClip, or PASCAL.  Abstracted patient characteristics reflect this entire cohort, as the provided BL characteristics were not stratified by device.

    Primary endpoint:
    Residual TR ≥ severe, within 30 days, n (%): 35 (24.1)

    Secondary endpoint:
    Procedural success (device placement and reduction of TR by ≥1 grade), n (%): 127 (87.6)

    Secondary endpoints:
    SLDA, n (%): 6 (4.1)

    Composite all-cause mortality and HF hospitalization, within 1 year, n (%): 39 (26.9)

    Other outcomes, procedurally, n (%):
    Periprocedural death: 0 (0)
    Conversion to surgery: 0 (0)
    Pericardial effusion or cardiac tamponade: 4 (2.8)
    Major bleeding: 10 (6.9)
    Stroke: 0 (0)

    αStudy quality assessed using the US Preventive Services Task Force’s Criteria for Assessing Internal Validity of Individual Studies tool
    *p<0.05; **p<0.01; ***p<0.001

    Abbreviations: 6MWT: 6-minute walk test; AE: adverse event; AST: aspartate transaminase; BL: baseline; CABG: coronary artery bypass graft; CAD: coronary artery disease; CI: confidence interval; CIED: cardiac implantable electronic device; COPD: chronic obstructive pulmonary disease; CRT: cardiac resynchronization therapy; CRT-D: CRT defibrillator; CV: cardiovascular; CVA: cerebrovascular accident; DBP: diastolic blood pressure; EQ-5D: EuroQol-5-dimension questionnaire; EROA: effective regurgitant orifice area; FAC: fractional area change; GFR: glomerular filtration rate; GI: gastrointestinal; HF: heart failure; HR: hazard ratio; HRQoL: health-related QoL; ICD: implantable cardioverter-defibrillator; ICU: intensive care unit; IQR: interquartile range; ITT: intention-to-treat; IVC: inferior vena cava; KCCQ: Kansas City Cardiomyopathy Questionnaire; LV: left ventricular; LVEF: LV ejection fraction; LVOT: LV outflow tract; MAE: major AE; MI: myocardial infarction; MT: medical therapy; NA: not applicable; NR: not reported; NTproBNP: N-terminal pro-B-type natriuretic peptide; NYHA: New York Heart Association; OMT: optimal medical therapy; OR: odds ratio; PCI: percutaneous coronary intervention; PISA: proximal isovelocity surface area; PPM: permanent pacemaker; P-Y: patient-year; QoL: quality of life; RCT: randomized controlled trial; RV: right ventricular; RVCPi: right ventricular cardiac power index; RVFAC: right vent RVEDD: RV end diastolic dimension; SAE: serious AE; SBP: systolic blood pressure; SD: standard deviation; SF-36: 36-item Short Form Health Survey; SLDA: single leaflet device attachment; sPAP: systolic pulmonary artery pressure; TA: tricuspid valve annulus; TAPSE: tricuspid annular plane systolic excursion; TAVI: transcatheter aortic valve implantation; TDI: tissue Doppler imaging; TEE: transesophageal echocardiogram; TIA: transient ischemic attack; TTE: transthoracic echocardiogram; T-TEER: tricuspid valve transcatheter edge-to-edge repair; TR: tricuspid regurgitation; TV: tricuspid valve; VTI: velocity time integral; WR: win ratio



    Appendix C: Heart Failure Quality of Life and Functional Measures

    Measure Description References

    New York Heart Association (NYHA) classification

    Class and Patient Symptoms

    • I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.
    • II: Slight limitation of physical activity.  Comfortable at rest.  Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.
    • III: Marked limitation of physical activity.  Comfortable at rest.  Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.
    • IV: Symptoms of heart failure at rest.  Any physical activity causes further discomfort.

    https://doi.org/10.1161/CIR.0b013e31829e8807 Opens in a new window (see Table 4)

    https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure Opens in a new window

    The Criteria Committee of the New York Heart Association. (1994). Nomenclature and criteria for diagnosis of diseases of the heart and great vessels (9th ed.), Boston, Mass: Little & Brown.

    Kansas City Cardiomyopathy Questionnaire (KCCQ)

    The KCCQ captures how heart failure affects patients’ lives.  The KCCQ has a 2-week recall period and includes 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy. 

    https://doi.org/10.1016/S0735-1097(00)00531-3 Opens in a new window

    https://doi.org/10.1016/j.jacc.2020.09.542 Opens in a new window

    Short Form Health Survey (SF-36)

    The SF-36 is a self-reported outcome measure assessing the impact of health on an individual's everyday life.  Also, the survey can be administered by a trained interviewer in person or by telephone.  The SF-36 evolved from the Medical Outcomes Study.

    Eight domains:

    1. Limitations in physical activities because of health problems.
    2. Limitations in social activities because of physical or emotional problems
    3. Limitations in usual role activities because of physical health problems
    4. Bodily pain
    5. General mental health (psychological distress and well-being)
    6. Limitations in usual role activities because of emotional problems
    7. Vitality (energy and fatigue)
    8. General health perceptions

    https://doi.org/10.1097/00005650-199303000-00006 Opens in a new window

    https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form/survey-instrument.html Opens in a new window

    Ware, J. E., Jr, & Sherbourne, C. D. (1992).  The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care30(6), 473–483.

    https://doi.org/10.1136/bmj.305.6846.160 Opens in a new window

    6-minute walk distance (6MWD)

    The six-minute walk test is a simple cardiopulmonary functional testing modality.  Its results can help ascertain the degree of functional impairment.

    https://doi.org/10.1177%2F1753944719870084 Opens in a new window

    https://www.ncbi.nlm.nih.gov/books/NBK576420/ Opens in a new window

    Katz Index of Independence in Activities of Daily Living

    The Katz Index of Independence in Activities of Daily Living assesses functional status as a measurement of the patient’s ability to perform activities of daily living (ADL) independently.  It quantifies ADL across a wide range of patient populations.

    https://doi.org/10.1002/acr.20638

    Minnesota Living with Heart Failure Questionnaire (MLHFQ)

    The Minnesota Living with Heart Failure Questionnaire (MLHFQ) assesses health-related quality of life for patients living with heart failure.  Questions focus on the physical, emotional and socioeconomic ways heart failure adversely affects patients. 

    https://doi.org/10.1186/s12955-016-0425-7 Opens in a new window

    https://license.umn.edu/product/minnesota-living-with-heart-failure-questionnaire-mlhfq


    [1] CMS’ CED Guidance Document (2024) Opens in a new window, 2, 3.

    [2] CMS’ CED Guidance Document (2024) Opens in a new window, 4

    [3] CMS’ CED Guidance Document (2024) Opens in a new window, 6.  This document also contains information on the purpose, principles, and process of CED.

  • Bibliography

    Adamo, M., Chioncel, O., Pagnesi, M., Bayes-Genis, A., Abdelhamid, M., Anker, S. D., Antohi, E. L., Badano, L., Ben Gal, T., Böhm, M., Delgado, V., Dreyfus, J., Faletra, F. F., Farmakis, D., Filippatos, G., Grapsa, J., Gustafsson, F., Hausleiter, J., Jaarsma, T., Karam, N., … Metra, M. (2024). Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC. European Journal of Heart Failure, 26(1), 18–33. https://doi.org/10.1002/ejhf.3106

    Alachkar, M. N., Schnupp, S., Eichelsdoerfer, A., Milzi, A., Mady, H., Salloum, B., Bisht, O., Cheikh-Ibrahim, M., Forkmann, M., Krygier, L., & Mahnkopf, C. (2023). Feasibility and Efficacy of TranscatheterTricuspid Valve Repair in Patients with Cardiac Implanted Electrical Devices and Trans-Tricuspid Leads. Journal of Clinical Medicine, 12(15), 4930. https://doi.org/10.3390/jcm12154930

    Alperi, A., Avanzas, P., Almendárez, M., León, V., Hernández-Vaquero, D., Silva, I., Fernández Del Valle, D., Fernández, F., Díaz, R., Rodes-Cabau, J., Morís, C., & Pascual, I. (2023). Early and mid-term outcomes of transcatheter tricuspid valve repair: systematic review and meta-analysis of observational studies. Revista Espanola de Cardiologia (English ed.), 76(5), 322–332. https://doi.org/10.1016/j.rec.2022.06.004

    Alqahtani, F., Berzingi, C. O., Aljohani, S., Hijazi, M., Al-Hallak, A., & Alkhouli, M. (2017). Contemporary Trends in the Use and Outcomes of Surgical Treatment of Tricuspid Regurgitation. Journal of the American Heart Association, 6(12), e007597. https://doi.org/10.1161/JAHA.117.007597

    American Heart Association. (2023, June 7). Classes and Stages of Heart Failure.  https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure

    Arnold, S. V., Goates, S., Sorajja, P., Adams, D. H., von Bardeleben, R. S., Kapadia, S. R., Cohen, D. J., & TRILUMINATE Pivotal Trial Investigators (2024). Health Status After Transcatheter Tricuspid-Valve Repair in Patients With Severe Tricuspid Regurgitation. Journal of the American College of Cardiology, 83(1), 1–13. https://doi.org/10.1016/j.jacc.2023.10.008

    Awtry, J., Newell, P., Vinholo, T. F., Harloff, M., Kerolos, M., Manful, A., Dey, T., Kaneko, T., & Sabe, A. (2023). The Relation Between Hospital Transcatheter Aortic Valve Replacement Volume and Transcatheter Edge-to-Edge Repair Outcomes: A Study Using the National Readmissions Database. The American Journal of Cardiology, 211, 228–235. https://doi.org/10.1016/j.amjcard.2023.10.006

    Badwan, O., Mirzai, S., Skoza, W., Hawk, F., Braghieri, L., Persits, I., Krishnaswamy, A., Puri, R., & Kapadia, S. R. (2023). Clinical outcomes following tricuspid transcatheter edge-to-edge repair with PASCAL: A meta-analysis. International Journal of Cardiology, 389, 131194. https://doi.org/10.1016/j.ijcard.2023.131194

    Barker, C. M., Kemp, L. S., Mancilla, M., Mollenkopf, S., Gunnarsson, C., Ryan, M., & David, G. (2024). Inequities in Access to Tricuspid Valve Treatments: The Impact of Procedure and Volume Requirements. JACC. Advances, 3(11), 101342. https://doi.org/10.1016/j.jacadv.2024.101342

    Bavaria, J. E., Tommaso, C. L., Brindis, R. G., Carroll, J. D., Deeb, G. M., Feldman, T. E., Gleason, T. G., Horlick, E. M., Kavinsky, C. J., Kumbhani, D. J., Miller, D. C., Seals, A. A., Shahian, D. M., Shemin, R. J., Sundt, T. M., 3rd, & Thourani, V. H. (2019). 2018 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document: Operator and Institutional Recommendations and Requirements for Transcatheter Aortic Valve Replacement: A Joint Report of the American Association for Thoracic Surgery, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Journal of the American College of Cardiology, 73(3), 340–374. https://doi.org/10.1016/j.jacc.2018.07.002

    Bilbao, A., Escobar, A., García-Perez, L., Navarro, G., & Quirós, R. (2016). The Minnesota living with heart failure questionnaire: comparison of different factor structures. Health and quality of life outcomes, 14, 23. https://doi.org/10.1186/s12955-016-0425-7

    Brazier, J. E., Harper, R., Jones, N. M., O'Cathain, A., Thomas, K. J., Usherwood, T., & Westlake, L. (1992). Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ (Clinical Research Ed.), 305(6846), 160–164. https://doi.org/10.1136/bmj.305.6846.160

    Butler, J., Khan, M. S., Mori, C., Filippatos, G. S., Ponikowski, P., Comin-Colet, J., Roubert, B., Spertus, J. A., & Anker, S. D. (2020). Minimal clinically important difference in quality of life scores for patients with heart failure and reduced ejection fraction. European Journal of Heart Failure, 22(6), 999–1005. https://doi.org/10.1002/ejhf.1810

    Cahill, T. J., Prothero, A., Wilson, J., Kennedy, A., Brubert, J., Masters, M., Newton, J. D., Dawkins, S., Enriquez-Sarano, M., Prendergast, B. D., & Myerson, S. G. (2021). Community prevalence, mechanisms and outcome of mitral or tricuspid regurgitation. Heart (British Cardiac Society), 107(12), 1003–1009. https://doi.org/10.1136/heartjnl-2020-318482

    Chang, C. C., Veen, K. M., Hahn, R. T., Bogers, A. J. J. C., Latib, A., Oei, F. B. S., Abdelghani, M., Modolo, R., Ho, S. Y., Abdel-Wahab, M., Fattouch, K., Bosmans, J., Caliskan, K., Taramasso, M., Serruys, P. W., Bax, J. J., van Mieghem, N. M. D. A., Takkenberg, J. J. M., Lurz, P., Modine, T., … Soliman, O. (2020). Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review. European Heart Journal, 41(20), 1932–1940. https://doi.org/10.1093/eurheartj/ehz614

    Chen, J., Cheng, Z., Dong, N., Dong, L., Guo, H., Guo, Y., Huang, H., Jiang, S., Lu, F., Li, F., Liu, J., Liu, L., Li, X., Mei, J., Ma, L., Qiao, C., Sun, L., Tu, G., Tao, L., Wang, D., … CMICS (2023). 2022 CMICS Expert Consensus on the Management of Isolated Tricuspid Regurgitation after Left-Sided Valve Surgery. Reviews in Cardiovascular Medicine, 24(5), 129. https://doi.org/10.31083/j.rcm2405129

    Chen, Q., Bowdish, M. E., Malas, J., Roach, A., Gill, G., Rowe, G., Thomas, J., Emerson, D., Trento, A., Egorova, N., & Chikwe, J. (2023). Isolated Tricuspid Operations: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis. The Annals of Thoracic Surgery, 115(5), 1162–1170. https://doi.org/10.1016/j.athoracsur.2022.12.041

    Cheng, L. J., Tan, R. L., & Luo, N. (2021). Measurement Properties of the EQ VAS Around the Globe: A Systematic Review and Meta-Regression Analysis. Value in Health: The Journal of the International Society for Pharmacoeconomics and Outcomes Research, 24(8), 1223–1233. https://doi.org/10.1016/j.jval.2021.02.003

    Chhatriwalla, A. K., Vemulapalli, S., Szerlip, M., Kodali, S., Hahn, R. T., Saxon, J. T., Mack, M. J., Ailawadi, G., Rymer, J., Manandhar, P., Kosinski, A. S., & Sorajja, P. (2019). Operator Experience and Outcomes of Transcatheter Mitral Valve Repair in the United States. Journal of the American College of Cardiology, 74(24), 2955–2965. https://doi.org/10.1016/j.jacc.2019.09.014

    Chorin, E., Rozenbaum, Z., Topilsky, Y., Konigstein, M., Ziv-Baran, T., Richert, E., Keren, G., & Banai, S. (2020). Tricuspid regurgitation and long-term clinical outcomes. European Heart Journal. Cardiovascular Imaging, 21(2), 157–165. https://doi.org/10.1093/ehjci/jez216

    Coisne, A., Scotti, A., Taramasso, M., Granada, J. F., Ludwig, S., Rodés-Cabau, J., Lurz, P., Hausleiter, J., Fam, N., Kodali, S. K., Pozzoli, A., Alessandrini, H., Biasco, L., Brochet, E., Denti, P., Estevez-Loureiro, R., Frerker, C., Ho, E. C., Monivas, V., Nickenig, G., … Latib, A. (2023). Prognostic Value of Tricuspid Valve Gradient After Transcatheter Edge-to-Edge Repair: Insights From the TriValve Registry. JACC. Cardiovascular Interventions, S1936-8798(23)00452-1. Advance online publication. https://doi.org/10.1016/j.jcin.2023.01.375

    Condello, F., Gitto, M., & Stefanini, G. G. (2021). Etiology, epidemiology, pathophysiology and management of tricuspid regurgitation: an overview. Reviews in Cardiovascular Medicine, 22(4), 1115–1142. https://doi.org/10.31083/j.rcm2204122

    Dannenberg, V., Bartko, P. E., Andreas, M., Bartunek, A., Goncharov, A., Gerçek, M., Friedrichs, K., Hengstenberg, C., Rudolph, V., & Ivannikova, M. (2024). Tricuspid edge-to-edge repair for tricuspid valve prolapse and flail leaflet: feasibility in comparison to patients with secondary tricuspid regurgitation. European Heart Journal. Cardiovascular Imaging, 25(3), 365–372. https://doi.org/10.1093/ehjci/jead264

    Davidson, L. J., Tang, G. H. L., Ho, E. C., Fudim, M., Frisoli, T., Camaj, A., Bowers, M. T., Masri, S. C., Atluri, P., Chikwe, J., Mason, P. J., Kovacic, J. C., Dangas, G. D., & American Heart Association Interventional Committee of the Council on Clinical Cardiology; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular Surgery and Anesthesia; and Council on Cardiovascular and Stroke Nursing (2024). The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association. Circulation, 149(22), e1223–e1238. https://doi.org/10.1161/CIR.0000000000001232

    Donal, E., Sitges, M., Panis, V., Schueler, R., Lapp, H., Moellmann, H., Nickenig, G., Bekeredjian, R., Estevez-Loureiro, R., Atmowihardjo, I., Trusty, P., & Lurz, P. (2024). Characterization of Tricuspid Valve Anatomy and Coaptation Gap in Subjects Receiving Tricuspid Transcatheter Edge-To-Edge Repair: Observations From the bRIGHT TriClip Study. Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography, 37(4), 397–404. https://doi.org/10.1016/j.echo.2023.12.002

    Donal, E., Dreyfus, J., Leurent, G., Coisne, A., Leroux, P. Y., Ganivet, A., Sportouch, C., Lavie-Badie, Y., Guerin, P., Rouleau, F., Diakov, C., van der Heyden, J., Lafitte, S., Obadia, J. F., Nejjari, M., Karam, N., Bernard, A., Neylon, A., Pierrard, R., Tchetche, D., … Tri-Fr Investigators (2025). Transcatheter Edge-to-Edge Repair for Severe Isolated Tricuspid Regurgitation: The Tri.Fr Randomized Clinical Trial. JAMA, 333(2), 124–132. https://doi.org/10.1001/jama.2024.21189

    Dreyfus, J., Flagiello, M., Bazire, B., Eggenspieler, F., Viau, F., Riant, E., Mbaki, Y., Bohbot, Y., Eyharts, D., Senage, T., Dubrulle, H., Nicol, M., Doguet, F., Nguyen, V., Coisne, A., Le Tourneau, T., Lavie-Badie, Y., Tribouilloy, C., Donal, E., Tomasi, J., … Messika-Zeitoun, D. (2020). Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes. European Heart Journal, 41(45), 4304–4317. https://doi.org/10.1093/eurheartj/ehaa643

    EuroQol Research Foundation. (2024). EQ-5D-5L. https://euroqol.org/information-and-support/euroqol-instruments/eq-5d-5l/

    Faller, J. W., Pereira, D. D. N., de Souza, S., Nampo, F. K., Orlandi, F. S., & Matumoto, S. (2019). Instruments for the detection of frailty syndrome in older adults: A systematic review. PloS One, 14(4), e0216166. https://doi.org/10.1371/journal.pone.0216166

    Fender, E. A., Zack, C. J., & Nishimura, R. A. (2018). Isolated tricuspid regurgitation: outcomes and therapeutic interventions. Heart (British Cardiac Society), 104(10), 798–806. https://doi.org/10.1136/heartjnl-2017-311586

    Feng, Y., Devlin, N., & Herdman, M. (2015). Assessing the health of the general population in England: how do the three- and five-level versions of EQ-5D compare?. Health and Quality of Life Outcomes, 13, 171. https://doi.org/10.1186/s12955-015-0356-8

    Food and Drug Administration (FDA). (2024, April 1). Summary of Safety and Effectiveness Data (SSED): PMA P230007. https://www.accessdata.fda.gov/cdrh_docs/pdf23/P230007B.pdf

    Food and Drug Administration (FDA). (2024, June 4). February 13, 2024: Circulatory System Devices Panel of the Medical Devices Advisory Committee Meeting Announcement. https://www.fda.gov/advisory-committees/advisory-committee-calendar/february-13-2024-circulatory-system-devices-panel-medical-devices-advisory-committee-meeting

    Food and Drug Administration (FDA). (2024). TriClip™ G4 SYSTEM Instructions for Use. https://www.accessdata.fda.gov/cdrh_docs/pdf23/P230007C.pdf

    Freixa, X., Arzamendi, D., Del Trigo, M., Cepas-Guillén, P. L., Li, P., Sanchis, L., Barreiro, M., Regueiro, A., Baz, J. A., Asmarats, L., Calvo, F., Moñivas, V., Meduiña, I., Goicolea, J., Sitges, M., & Estévez-Loureiro, R. (2022). The TriClip system for edge-to-edge transcatheter tricuspid valve repair. A Spanish multicenter study. Revista Espanola de Cardiologia (English ed.), 75(10), 797–804. https://doi.org/10.1016/j.rec.2022.01.007

    Giannitsi, S., Bougiakli, M., Bechlioulis, A., Kotsia, A., Michalis, L. K., & Naka, K. K. (2019). 6-minute walking test: a useful tool in the management of heart failure patients. Therapeutic Advances in Cardiovascular Disease, 13, 1753944719870084. https://doi.org/10.1177/1753944719870084

    Goebel, B., Lurz, P., Schmitz, T., Bekeredjian, R., Nickenig, G., Mollmann, H., von Bardeleben, R. S., Schmeisser, A., Heitkemper, M., Atmowihardjo, I., Estévez-Loureiro, R., & Donal, E. (2025). Outcomes of tricuspid transcatheter edge-to-edge repair in subjects with endocardial leads. EuroIntervention : Journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 21(5), e253–e261. https://doi.org/10.4244/EIJ-D-23-01033

    Green, C. P., Porter, C. B., Bresnahan, D. R., & Spertus, J. A. (2000). Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. Journal of the American College of Cardiology, 35(5), 1245–1255. https://doi.org/10.1016/s0735-1097(00)00531-3

    Hahn, R. T., & Zamorano, J. L. (2017). The need for a new tricuspid regurgitation grading scheme. European Heart Journal. Cardiovascular Imaging, 18(12), 1342–1343. https://doi.org/10.1093/ehjci/jex139

    Hahn R. T. (2023). Tricuspid Regurgitation. The New England Journal of Medicine, 388(20), 1876–1891. https://doi.org/10.1056/NEJMra2216709

    Hahn, R. T., Lawlor, M. K., Davidson, C. J., Badhwar, V., Sannino, A., Spitzer, E., Lurz, P., Lindman, B. R., Topilsky, Y., Baron, S. J., Chadderdon, S., Khalique, O. K., Tang, G. H. L., Taramasso, M., Grayburn, P. A., Badano, L., Leipsic, J., Lindenfeld, J., Windecker, S., Vemulapalli, S., … Hausleiter, J. (2023). Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints. European Heart Journal, 44(43), 4508–4532. https://doi.org/10.1093/eurheartj/ehad653

    Hanses, U., Diehl, K., Ammar, A. B., Dierks, P., Alo, S., Fach, A., Schmucker, J., Frerker, C., Eitel, I., Wienbergen, H., Hambrecht, R., & Osteresch, R. (2023). Right Ventricular Cardiac Power Index Predicts 1 Year Outcome After Transcatheter Edge-to-Edge-Repair for Severe Tricuspid Valve Regurgitation. The American Journal of Cardiology, 202, 182–191. https://doi.org/10.1016/j.amjcard.2023.06.071

    Haurand, J. M., Kavsur, R., Ochs, L., Tanaka, T., Iliadis, C., Sugiura, A., Kelm, M., Nickenig, G., Baldus, S., Westenfeld, R., Becher, M. U., Pfister, R., & Horn, P. (2022). Deep sedation vs. general anesthesia for transcatheter tricuspid valve repair. Frontiers in Cardiovascular Medicine, 9, 976822. https://doi.org/10.3389/fcvm.2022.976822

    Hellhammer, K., Schueler, R., Eißmann, M., Schumacher, B., Wolf, A., Bruder, O., Schmitz, T., & Lambers, M. (2022). Safety of transesophageal echocardiography during transcatheter edge-to-edge tricuspid valve repair: A single-center experience. Frontiers in Cardiovascular Medicine, 9, 856028. https://doi.org/10.3389/fcvm.2022.856028

    Izumi, C., Eishi, K., Ashihara, K., Arita, T., Otsuji, Y., Kunihara, T., Komiya, T., Shibata, T., Seo, Y., Daimon, M., Takanashi, S., Tanaka, H., Nakatani, S., Ninami, H., Nishi, H., Hayashida, K., Yaku, H., Yamaguchi, J., Yamamoto, K., Watanabe, H., … Japanese Circulation Society Joint Working Group (2020). JCS/JSCS/JATS/JSVS 2020 Guidelines on the Management of Valvular Heart Disease. Circulation Journal: Official Journal of the Japanese Circulation Society, 84(11), 2037–2119. https://doi.org/10.1253/circj.CJ-20-0135

    Kar, S., Makkar, R. R., Whisenant, B. K., Hamid, N., Naik, H., Tadros, P., Price, M. J., Singh, G., Schwartz, J. G., Kapadia, S., Alli, O., Horr, S., Seshiah, P., Batchelor, W., Jones, B. M., Ahmed, M. I., Benza, R., Jorde, U., Thourani, V. H., Ghobrial, A. A., … TRILUMINATE pivotal investigators (2025). Two-year Outcomes of Transcatheter Edge-to-edge Repair for Severe Tricuspid Regurgitation: The TRILUMINATE Pivotal Randomized Trial. Circulation, 10.1161/CIRCULATIONAHA.125.074536. Advance online publication. https://doi.org/10.1161/CIRCULATIONAHA.125.074536

    Kazum, S. S., Sagie, A., Shochat, T., Ben-Gal, T., Bental, T., Kornowski, R., Shapira, Y., Vaturi, M., & Hasin, T. (2019). Prevalence, Echocardiographic Correlations, and Clinical Outcome of Tricuspid Regurgitation in Patients with Significant Left Ventricular Dysfunction. The American Journal of Medicine, 132(1), 81–87. https://doi.org/10.1016/j.amjmed.2018.10.004

    Kodali, S. K., Hahn, R. T., Davidson, C. J., Narang, A., Greenbaum, A., Gleason, P., Kapadia, S., Miyasaka, R., Zahr, F., Chadderdon, S., Smith, R. L., Grayburn, P., Kipperman, R. M., Marcoff, L., Whisenant, B., Gonzales, M., Makkar, R., Makar, M., O'Neill, W., Wang, D. D., … Eleid, M. F. (2023). 1-Year Outcomes of Transcatheter Tricuspid Valve Repair. Journal of the American College of Cardiology, 81(18), 1766–1776. https://doi.org/10.1016/j.jacc.2023.02.049

    Little, S. H., Rigolin, V. H., Garcia-Sayan, E., Hahn, R. T., Hung, J., Mackensen, G. B., Mankad, S., Quader, N., & Saric, M. (2023). Recommendations for Special Competency in Echocardiographic Guidance of Structural Heart Disease Interventions: From the American Society of Echocardiography. Journal of the American Society of Echocardiography: Official Publication of the American Society of Echocardiography, 36(4), 350–365. https://doi.org/10.1016/j.echo.2023.01.014

    Lurz, P., Stephan von Bardeleben, R., Weber, M., Sitges, M., Sorajja, P., Hausleiter, J., Denti, P., Trochu, J. N., Nabauer, M., Tang, G. H. L., Biaggi, P., Ying, S. W., Trusty, P. M., Dahou, A., Hahn, R. T., Nickenig, G., & TRILUMINATE Investigators (2021). Transcatheter Edge-to-Edge Repair for Treatment of Tricuspid Regurgitation. Journal of the American College of Cardiology, 77(3), 229–239. https://doi.org/10.1016/j.jacc.2020.11.038

    Lurz, P., Besler, C., Schmitz, T., Bekeredjian, R., Nickenig, G., Möllmann, H., von Bardeleben, R. S., Schmeisser, A., Atmowihardjo, I., Estevez-Loureiro, R., Lubos, E., Heitkemper, M., Huang, D., Lapp, H., Donal, E., & bRIGHT PAS Principal Investigators (2023). Short-Term Outcomes of Tricuspid Edge-to-Edge Repair in Clinical Practice. Journal of the American College of Cardiology, 82(4), 281–291. https://doi.org/10.1016/j.jacc.2023.05.008

    Lurz, P., Rommel, K. P., Schmitz, T., Bekeredjian, R., Nickenig, G., Möllmann, H., von Bardeleben, R. S., Schmeisser, A., Atmowihardjo, I., Estevez-Loureiro, R., Lubos, E., Heitkemper, M., Peterman, K., Lapp, H., & Donal, E. (2024). Real-World 1-Year Results of Tricuspid Edge-to-Edge Repair From the bRIGHT Study. Journal of the American College of Cardiology, 84(7), 607–616. https://doi.org/10.1016/j.jacc.2024.05.006

    Mattig, I., Barbieri, F., Kasner, M., Romero Dorta, E., Heinrich-Schüler, A. L., Zhu, M., Stangl, K., Landmesser, U., Reinthaler, M., & Dreger, H. (2023). Comparison of procedural characteristics of percutaneous annuloplasty and edge-to-edge repair for the treatment of severe tricuspid regurgitation. Frontiers in Cardiovascular Medicine, 10, 1232327. https://doi.org/10.3389/fcvm.2023.1232327

    Matos Casano, H. A., & Anjum, F. (2023). Six-Minute Walk Test. In StatPearls. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK576420/

    McHorney, C. A., Ware, J. E., Jr, & Raczek, A. E. (1993). The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Medical Care, 31(3), 247–263. https://doi.org/10.1097/00005650-199303000-00006

    Messika-Zeitoun, D., Baumgartner, H., Burwash, I. G., Vahanian, A., Bax, J., Pibarot, P., Chan, V., Leon, M., Enriquez-Sarano, M., Mesana, T., & Iung, B. (2023). Unmet needs in valvular heart disease. European Heart Journal, 44(21), 1862–1873. https://doi.org/10.1093/eurheartj/ehad121

    Mulla, S., Asuka, E., Bora, V., Sharma, S., & Siddiqui, W. J. (2024). Tricuspid Regurgitation. In StatPearls. StatPearls Publishing.

    Naik, H., Price, M. J., Kapadia, S., Whisenant, B. K., Tadros, P., Makkar, R., Asgar, A. W., Fam, N., Tang, G. H. L., Mehta, S. R., Byrne, T., Singh, G., Panaich, S. S., Peterman, K., Trusty, P. M., Hamid, N., Hahn, R. T., Adams, D. H., & Sorajja, P. (2025). Tricuspid Transcatheter Edge-to-Edge Repair in Patients With Transvalvular CIED Leads: The TRILUMINATE Pivotal Trial. JACC. Clinical electrophysiology, S2405-500X(25)00010-6. Advance online publication. https://doi.org/10.1016/j.jacep.2025.01.001

    Nickenig, G., Weber, M., Lurz, P., von Bardeleben, R. S., Sitges, M., Sorajja, P., Hausleiter, J., Denti, P., Trochu, J. N., Näbauer, M., Dahou, A., & Hahn, R. T. (2019). Transcatheter edge-to-edge repair for reduction of tricuspid regurgitation: 6-month outcomes of the TRILUMINATE single-arm study. Lancet (London, England), 394(10213), 2002–2011. https://doi.org/10.1016/S0140-6736(19)32600-5

    Offen, S., Playford, D., Strange, G., Stewart, S., & Celermajer, D. S. (2022). Adverse Prognostic Impact of Even Mild or Moderate Tricuspid Regurgitation: Insights from the National Echocardiography Database of Australia. Journal of the American Society of Echocardiography: Official Publication of the American Society of Echocardiography, 35(8), 810–817. https://doi.org/10.1016/j.echo.2022.04.003

    Otto, C. M., Nishimura, R. A., Bonow, R. O., Carabello, B. A., Erwin, J. P., 3rd, Gentile, F., Jneid, H., Krieger, E. V., Mack, M., McLeod, C., O'Gara, P. T., Rigolin, V. H., Sundt, T. M., 3rd, Thompson, A., & Toly, C. (2021). 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology, 77(4), e25–e197. https://doi.org/10.1016/j.jacc.2020.11.018

    Patrascu, A. I., Binder, D., Alashkar, I., Schnabel, P., Stähle, W., Weinmann, K., Schneider, J., Conzelmann, L. O., Mehlhorn, U., & Ott, I. (2022). Transcatheter Tricuspid Valve Repair in Prohibitive Risk Patients: Impact on Quality of Life and Major Organ Systems. The Canadian Journal of Cardiology, 38(12), 1921–1931. https://doi.org/10.1016/j.cjca.2022.09.006

    Prihadi, E. A., Delgado, V., Leon, M. B., Enriquez-Sarano, M., Topilsky, Y., & Bax, J. J. (2019). Morphologic Types of Tricuspid Regurgitation: Characteristics and Prognostic Implications. JACC. Cardiovascular Imaging, 12(3), 491–499. https://doi.org/10.1016/j.jcmg.2018.09.027

    RAND. (n.d.). 36-Item Short Form Survey Instrument (SF-36). https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form/survey-instrument.html

    Rdzanek, A., Szymański, P., Gackowski, A., Scisło, P., Pręgowski, J., Pietrasik, A., Trębacz, J., Zbroński, K., Kochman, J., Witkowski, A., Wojakowski, W., & Grygier, M. (2021). Percutaneous tricuspid edge-to-edge repair - patient selection, imaging considerations, and the procedural technique. Expert opinion of the Working Group on Echocardiography and Association of CardioVascular Interventions of the Polish Cardiac Society. Kardiologia Polska, 79(10), 1178–1191. https://doi.org/10.33963/KP.a2021.0125

    Ricci, F., Bufano, G., Galusko, V., Sekar, B., Benedetto, U., Awad, W. I., Di Mauro, M., Gallina, S., Ionescu, A., Badano, L., & Khanji, M. Y. (2022). Tricuspid regurgitation management: a systematic review of clinical practice guidelines and recommendations. European Heart Journal. Quality of Care & Clinical Outcomes, 8(3), 238–248. https://doi.org/10.1093/ehjqcco/qcab081

    Rockwood, K., Song, X., MacKnight, C., Bergman, H., Hogan, D. B., McDowell, I., & Mitnitski, A. (2005). A global clinical measure of fitness and frailty in elderly people. CMAJ: Canadian Medical Association Journal, 173(5), 489–495. https://doi.org/10.1503/cmaj.050051

    Russo, G., Badano, L. P., Adamo, M., Alessandrini, H., Andreas, M., Braun, D., Connelly, K. A., Denti, P., Estevez-Loureiro, R., Fam, N., Gavazzoni, M., Hahn, R. T., Harr, C., Hausleiter, J., Himbert, D., Kalbacher, D., Ho, E., Latib, A., Lubos, E., Ludwig, S., … Taramasso, M. (2023). Characteristics and outcomes of patients with atrial versus ventricular secondary tricuspid regurgitation undergoing tricuspid transcatheter edge-to-edge repair - Results from the TriValve registry. European Journal of Heart Failure, 25(12), 2243–2251. https://doi.org/10.1002/ejhf.3075

    Salemi, A., Sedrakyan, A., Mao, J., Elmously, A., Wijeysundera, H., Tam, D. Y., Di Franco, A., Redwood, S., Girardi, L. N., Fremes, S. E., & Gaudino, M. (2019). Individual Operator Experience and Outcomes in Transcatheter Aortic Valve Replacement. JACC. Cardiovascular Interventions, 12(1), 90–97. https://doi.org/10.1016/j.jcin.2018.10.030

    Scotti, A., Sturla, M., Granada, J. F., Kodali, S. K., Coisne, A., Mangieri, A., Godino, C., Ho, E., Goldberg, Y., Chau, M., Jorde, U. P., Garcia, M. J., Maisano, F., Bapat, V. N., Ailawadi, G., & Latib, A. (2022). Outcomes of isolated tricuspid valve replacement: a systematic review and meta-analysis of 5,316 patients from 35 studies. EuroIntervention: Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 18(10), 840–851. https://doi.org/10.4244/EIJ-D-22-00442

    Shimoda, T. M., Ueyama, H. A., Miyamoto, Y., Watanabe, A., Gotanda, H., Kolte, D., Latib, A., Kaneko, T., Zajarias, A., Elmariah, S., Takayama, H., Tsugawa, Y., & Kuno, T. (2025). Comparison of Transcatheter Versus Surgical Tricuspid Repair Among Patients With Tricuspid Regurgitation: Two-Year Results. Circulation. Cardiovascular interventions, 18(1), e014825. https://doi.org/10.1161/CIRCINTERVENTIONS.124.014825

    Siddiqui, H. F., Khan, A. B., Nasir, M. M., Latif, F., Siddiqui, A. F., Akhtar, P., Hamza, M., & Barmanwalla, A. (2023). Therapeutic Outcomes Following Isolated Transcatheter Tricuspid Valve Repair: A Systematic Review and Meta-analysis. Current Problems in Cardiology, 48(12), 101985. https://doi.org/10.1016/j.cpcardiol.2023.101985

    Singh, J. P., Evans, J. C., Levy, D., Larson, M. G., Freed, L. A., Fuller, D. L., Lehman, B., & Benjamin, E. J. (1999). Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study). The American Journal of Cardiology, 83(6), 897–902. https://doi.org/10.1016/s0002-9149(98)01064-9

    Sorajja, P., Whisenant, B., Hamid, N., Naik, H., Makkar, R., Tadros, P., Price, M. J., Singh, G., Fam, N., Kar, S., Schwartz, J. G., Mehta, S., Bae, R., Sekaran, N., Warner, T., Makar, M., Zorn, G., Spinner, E. M., Trusty, P. M., Benza, R., … TRILUMINATE Pivotal Investigators (2023). Transcatheter Repair for Patients with Tricuspid Regurgitation. The New England Journal of Medicine, 388(20), 1833–1842. https://doi.org/10.1056/NEJMoa2300525

    Spertus, J. A., Jones, P. G., Sandhu, A. T., & Arnold, S. V. (2020). Interpreting the Kansas City Cardiomyopathy Questionnaire in Clinical Trials and Clinical Care: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 76(20), 2379–2390. https://doi.org/10.1016/j.jacc.2020.09.542

    Stolz, L., Doldi, P. M., Kresoja, K. P., Bombace, S., Koell, B., Kassar, M., Kirchner, J., Weckbach, L. T., Ludwig, S., Stocker, T. J., Glaser, H., Schöber, A. R., Massberg, S., Näbauer, M., Rudolph, V., Kalbacher, D., Praz, F., Lurz, P., & Hausleiter, J. (2024). Applying the TRILUMINATE Eligibility Criteria to Real-World Patients Receiving Tricuspid Valve Transcatheter Edge-to-Edge Repair. JACC. Cardiovascular Interventions, 17(4), 535–548. https://doi.org/10.1016/j.jcin.2023.11.014

    Stolz, L., Kresoja, K. P., von Stein, J., Fortmeier, V., Koell, B., Rottbauer, W., Kassar, M., Goebel, B., Denti, P., Achouh, P., Rassaf, T., Barreiro-Perez, M., Boekstegers, P., Rück, A., Doldi, P. M., Novotny, J., Zdanyte, M., Adamo, M., Vincent, F., Schlegel, P., …  on behalf of the EuroTR Investigators (2024). Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry. European journal of heart failure, 26(8), 1850–1860. https://doi.org/10.1002/ejhf.3274

    Sugiura, A., Tanaka, T., Kavsur, R., Öztürk, C., Vogelhuber, J., Wilde, N., Becher, M. U., Zimmer, S., Nickenig, G., & Weber, M. (2021). Leaflet Configuration and Residual Tricuspid Regurgitation After Transcatheter Edge-to-Edge Tricuspid Repair. JACC. Cardiovascular Interventions, 14(20), 2260–2270. https://doi.org/10.1016/j.jcin.2021.07.048

    Tanaka, T., Sugiura, A., Kavsur, R., Öztürk, C., Wilde, N., Zimmer, S., Nickenig, G., Weber, M., & Vogelhuber, J. (2024). Changes in right ventricular function and clinical outcomes following tricuspid transcatheter edge-to-edge repair. European Journal of Heart Failure, 26(4), 1015–1024. https://doi.org/10.1002/ejhf.3183

    Tang, G. H. L., Hahn, R. T., Whisenant, B. K., Hamid, N., Naik, H., Makkar, R. R., Tadros, P., Price, M. J., Singh, G. D., Fam, N. P., Kar, S., Mehta, S. R., Bae, R., Sekaran, N. K., Warner, T., Makar, M., Zorn, G., Benza, R., Jorde, U. P., McCarthy, P. M., … TRILUMINATE Pivotal Investigators (2025). Tricuspid Transcatheter Edge-to-Edge Repair for Severe Tricuspid Regurgitation: 1-Year Outcomes From the TRILUMINATE Randomized Cohort. Journal of the American College of Cardiology, 85(3), 235–246. https://doi.org/10.1016/j.jacc.2024.10.086

    The Criteria Committee of the New York Heart Association. (1994). Nomenclature and criteria for diagnosis of diseases of the heart and great vessels (9th ed.), Boston, Mass: Little & Brown.

    Thourani, V. H., Bonnell, L., Wyler von Ballmoos, M. C., Mehaffey, J. H., Bowdish, M., Kurlansky, P., Jacobs, J. P., O'Brien, S., Shahian, D. M., & Badhwar, V. (2024). Outcomes of Isolated Tricuspid Valve Surgery: A Society of Thoracic Surgeons Analysis and Risk Model. The Annals of Thoracic Surgery, 118(4), 873–881. https://doi.org/10.1016/j.athoracsur.2024.04.014

    University of Minnesota. (n.d.). Minnesota LIVING WITH HEART FAILURE® Questionnaire (MLHFQ). https://license.umn.edu/product/minnesota-living-with-heart-failure-questionnaire-mlhfq

    Vahanian, A., Beyersdorf, F., Praz, F., Milojevic, M., Baldus, S., Bauersachs, J., Capodanno, D., Conradi, L., De Bonis, M., De Paulis, R., Delgado, V., Freemantle, N., Gilard, M., Haugaa, K. H., Jeppsson, A., Jüni, P., Pierard, L., Prendergast, B. D., Sádaba, J. R., Tribouilloy, C., … ESC/EACTS Scientific Document Group (2022). 2021 ESC/EACTS Guidelines for the management of valvular heart disease. European Heart Journal, 43(7), 561–632. https://doi.org/10.1093/eurheartj/ehab395

    Vassileva, C. M., McNeely, C., Spertus, J., Markwell, S., & Hazelrigg, S. (2015). Hospital volume, mitral repair rates, and mortality in mitral valve surgery in the elderly: an analysis of US hospitals treating Medicare fee-for-service patients. The Journal of Thoracic and Cardiovascular Surgery, 149(3), 762–768.e1. https://doi.org/10.1016/j.jtcvs.2014.08.084

    Vemulapalli, S., Carroll, J. D., Mack, M. J., Li, Z., Dai, D., Kosinski, A. S., Kumbhani, D. J., Ruiz, C. E., Thourani, V. H., Hanzel, G., Gleason, T. G., Herrmann, H. C., Brindis, R. G., & Bavaria, J. E. (2019). Procedural Volume and Outcomes for Transcatheter Aortic-Valve Replacement. The New England Journal of Medicine, 380(26), 2541–2550. https://doi.org/10.1056/NEJMsa1901109

    Vemulapalli, S., Prillinger, J. B., & Adams, D. H. (2025). How Procedural Volume Prerequisites Could Impact Access to Tricuspid Transcatheter Edge-to-Edge Repair. JACC. Cardiovascular interventions, S1936-8798(25)00612-0. Advance online publication. https://doi.org/10.1016/j.jcin.2025.01.444

    Vogelhuber, J., Tanaka, T., Kavsur, R., Goto, T., Öztürk, C., Silaschi, M., Nickenig, G., Zimmer, S., Weber, M., & Sugiura, A. (2024). Outcomes of Transcatheter Tricuspid Edge-to-Edge Repair in Patients With Right Ventricular Dysfunction. Circulation. Cardiovascular Interventions, 17(6), e013156. https://doi.org/10.1161/CIRCINTERVENTIONS.123.013156

    von Bardeleben, R. S., Lurz, P., Sorajja, P., Ruf, T., Hausleiter, J., Sitges, M., Da Rocha E Silva, J., Näbauer, M., Weber, M., Tang, G. H. L., Heitkemper, M., Ying, S. W., Trochu, J. N., Kar, S., Hahn, R. T., Nickenig, G., & TRILUMINATE Trial Investigators (2023). Two-Year Outcomes for Tricuspid Repair With a Transcatheter Edge-to-Edge Valve Repair From the Transatlantic TRILUMINATE Trial. Circulation. Cardiovascular Interventions, 16(8), e012888. https://doi.org/10.1161/CIRCINTERVENTIONS.122.012888

    Wang, T. K. M., Akyuz, K., Mentias, A., Kirincich, J., Duran Crane, A., Xu, S., Popovic, Z. B., Xu, B., Gillinov, A. M., Pettersson, G. B., Griffin, B. P., & Desai, M. Y. (2022). Contemporary Etiologies, Outcomes, and Novel Risk Score for Isolated Tricuspid Regurgitation. JACC. Cardiovascular Imaging, 15(5), 731–744. https://doi.org/10.1016/j.jcmg.2021.10.015

    Ware, J. E., Jr, & Sherbourne, C. D. (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care, 30(6), 473–483.

    White, D. K., Wilson, J. C., & Keysor, J. J. (2011). Measures of adult general functional status: SF-36 Physical Functioning Subscale (PF-10), Health Assessment Questionnaire (HAQ), Modified Health Assessment Questionnaire (MHAQ), Katz Index of Independence in activities of daily living, Functional Independence Measure (FIM), and Osteoarthritis-Function-Computer Adaptive Test (OA-Function-CAT). Arthritis Care & Research, 63 Suppl 11, S297–S307. https://doi.org/10.1002/acr.20638

    Wild, M. G., Stolz, L., Rosch, S., Rudolph, F., Goebel, B., Köll, B., von Stein, P., Rottbauer, W., Rassaf, T., Beucher, H., Kraus, M., Kassar, M., Geisler, T., Rück, A., Ferreira-Martins, J., Toggweiler, S., Sagmeister, P., Westermann, D., Stocker, T. J., Weckbach, L. T., … PASTE Investigators (2025). Transcatheter Valve Repair for Tricuspid Regurgitation: 1-Year Results From a Large European Real-World Registry. Journal of the American College of Cardiology, 85(3), 220–231. https://doi.org/10.1016/j.jacc.2024.10.068

    Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Jr, Drazner, M. H., Fonarow, G. C., Geraci, S. A., Horwich, T., Januzzi, J. L., Johnson, M. R., Kasper, E. K., Levy, W. C., Masoudi, F. A., McBride, P. E., McMurray, J. J., Mitchell, J. E., Peterson, P. N., Riegel, B., Sam, F., … Wilkoff, B. L. (2013). 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation, 128(16), 1810–1852. https://doi.org/10.1161/CIR.0b013e31829e8807

    Zoghbi, W. A., Adams, D., Bonow, R. O., Enriquez-Sarano, M., Foster, E., Grayburn, P. A., Hahn, R. T., Han, Y., Hung, J., Lang, R. M., Little, S. H., Shah, D. J., Shernan, S., Thavendiranathan, P., Thomas, J. D., & Weissman, N. J. (2017). Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. Journal of the American Society of Echocardiography: Official Publication of the American Society of Echocardiography, 30(4), 303–371. https://doi.org/10.1016/j.echo.2017.01.007