Evaluating the Benefit of Concurrent Tricuspid Valve Repair During Mitral Surgery

The purpose of the research is to determine whether repairing a tricuspid valve (TV) in patients with mild to moderate tricuspid regurgitation (TR), at the time of planned mitral valve surgery (MVS), would improve the heart health of those who receive it compared to those who do not.

At this point, the medical community is split in their opinion on whether surgeons should routinely repair mild to moderate TR in patients who are undergoing planned mitral valve surgery, and this study will answer this question.

Study Overview

• Status: Completed
• Conditions: Tricuspid Regurgitation; Mild Tricuspid Regurgitation; Moderate Tricuspid Regurgitation
• Intervention / Treatment: Procedure: MVS; Procedure: TV Annuloplasty

Detailed Description

The tricuspid valve controls the flow of blood in your heart between the right ventricle and the right atrium. TR is a condition where the valve does not close fully when it is supposed to and blood can then leak back into the right atrium. When TR becomes severe, surgery is usually performed to correct it. The purpose of the research is to determine whether repairing a tricuspid valve in patients with mild to moderate TR, at the time of planned mitral valve surgery, would improve the heart health of those who receive it compared to those who do not. There are no new or "experimental" procedures being tested in this study: both the mitral valve procedure and the tricuspid valve repair procedure are well established surgeries and are regularly performed together in patients who have severe TR. The available evidence addressing this issue is not definite: it is based on less rigorous methods of investigation, and the results have been conflicting. The study being proposed here will use rigorous scientific methods and should result in a very high level of certainty about what surgical treatment is best for patients with your condition.

This study will enroll people scheduled for mitral valve surgery with mild to moderate tricuspid regurgitation.

• Study Type: Interventional
• Enrollment (Actual): 401
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
  • Alberta
    • Edmonton, Alberta, Canada, t6g2b7
      • University of Alberta Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5B 1W8
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre hospitalier de l'Université de Montréal
• Germany
  • Bad Oeynhausen, Germany
    • HDZ NRW Bad Oeynhausen
  • Berlin, Germany
    • Deutsches Herzzentrum Berlin
  • Freiburg, Germany
    • Heart Center, University of Freiburg
  • Munich, Germany
    • German Heart Center Munich
  • Brandenburg
    • Berlin, Brandenburg, Germany, 11353
      • Universitäres Herzzentrum Hamburg
    • Berlin, Brandenburg, Germany, 13347
      • Herzzentrum Leipzig
  • Hesse-Nassau
    • Frankfurt, Hesse-Nassau, Germany, 60590
      • University Hospital Frankfurt
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany
      • University Medical Center Göttingen
  • Thuringia
    • Jena, Thuringia, Germany
      • University Medical Center Jena
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8039
      • Yale University School of Medicine - Yale-New Haven Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Bethesda, Maryland, United States, 20814
      • Suburban Hospital
    • Columbia, Maryland, United States, 21044
      • MedStar Health
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Services
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Einstein Heart Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Stony Brook, New York, United States, 11790
      • Stony Brook Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Raleigh, North Carolina, United States, 27610
      • WakeMed Clinical Research Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States
      • Baylor College of Medicine
    • Plano, Texas, United States, 75093
      • Baylor Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health Systems
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Undergoing MVS for degenerative MR* with (a) Moderate TR as determined by transthoracic 2D echocardiography, or (b) Tricuspid annular dimension ≥ 40 mm (index: ≥21mm/M2 BSA) and none/trace or mild TR, determined by echocardiography.
• Age ≥ 18 years

• Able to sign Informed Consent and Release of Medical Information forms

  • "Degenerative mitral valve disease refers to a spectrum of conditions in which morphologic changes in the connective tissues of the mitral valve cause structural lesions . . ., such as chordal elongation, chordal rupture, leaflet tissue expansion, and annular dilation typically resulting in mitral regurgitation due to leaflet prolapse." This definition excludes rheumatic heart disease. (Anyanwu AC, Adams DH. (2007) Etiological classification of degenerative mitral valve disease: Barlow's disease and fibroelasticity deficiency. Semin Thorac Cardiovasc Surg; 19(2): 90-6).

Exclusion Criteria:

• Functional MR
• Evidence of sub-optimal fluid management (e.g., lack of diuretics, weight in excess of dry weight) in the opinion of the cardiology investigator
• Structural / organic TV disease
• Severe TV regurgitation as determined by preoperative transthoracic echocardiography (TTE)
• Implanted pacemaker or defibrillator, where the leads cross the TV from the right atrium into the right ventricle
• Concomitant cardiac surgery other than atrial fibrillation correction surgery (PVI, Maze, LAA closure), closure of PFO or ASD, or CABG
• Cardiogenic shock at the time of randomization
• STEMI requiring intervention within 7 days prior to randomization
• Evidence of cirrhosis or hepatic synthetic failure
• Severe, irreversible pulmonary hypertension in the judgment of the investigator
• Pregnancy at the time of randomization
• Therapy with an investigational intervention at the time of screening, or plan to enroll patient in additional investigational intervention study during participation in this trial
• Any concurrent disease with life expectancy < 2 years
• Unable or unwilling to provide informed consent
• Unable or unwilling to comply with study follow up in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MVS Alone; Participants will undergo mitral valve surgery alone.	Procedure: MVS; MVS will be performed using standard surgical techniques
Active Comparator: MVS + TV Annuloplasty; Patients will undergo mitral valve surgery and tricuspid valve annuloplasty.	Procedure: MVS; MVS will be performed using standard surgical techniques; Procedure: TV Annuloplasty; TV Annuloplasty will be performed using standard surgical techniques

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Failure	The primary outcome of this trial is treatment failure defined as the composite of (1) death from any cause, (2) reoperation for TR, (3) presence of severe TR at two years post randomization or, for patients enrolled with less than moderate TR and annular dilatation, progression by two grades (i.e., from none/trace TR to moderate TR) at two years post randomization.	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Artery Pressure	Pulmonary artery pressure assessed by echocardiography.	up to 24 Months
Survival	Incidence of participants alive	up to 60 Months
Length of Index Hospitalization		average 30 days
Number of Participants With Major Adverse Cardiac and Cerebrovascular Events (MACCE)	Major Adverse Cardiac and Cerebrovascular Events (MACCE) is defined as a non-weighted composite score comprised of the following components: Death, Stroke, and Serious heart failure events	up to 24 Months
Number of Participants With NYHA Classification I-IV	Functional status will be assessed by the New York Heart Association (NYHA) Classification scale which ranges from 1 (no physical limitations) to 4 (severe limitation of physical activity).; Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.; Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.; Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest.; Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.; No NYHA class listed or unable to determine	at 24 Months
Diuretic Use	The diuretic requirements of patients will be assessed.	24 Months
Six Minute Walk Test	The total distance, in feet, walked in six minutes	24 Months
Number of Participants With Degree of TR	Degree of TR assessed by echocardiography, categorized according to American Society of Echocardiography guidelines as none/mild/moderate/severe.	up to 24 Months
Right Ventricular Size		24 Months
Number of Participants With Normal RV Function	Number of Participants with Normal RV Function assessed by echocardiography.	up to 24 Months
Peak Tricuspid Annular Velocity		24 Months
Tricuspid Annular Peak Systolic Excursion (TAPSE)	Degree of RV function assessed by TAPSE	24 Months
Right Ventricular Fractional Area Change (RVFAC)	Degree of RV function assessed by RVFAC	24 Months
Right Ventricular Volume	RV Volume as measured by transthoracic 3D echocardiography.	24 Months
SF-12	Quality of Life assessed by SF-12. A measure of perceived health (health-related quality of life [QoL]) that describes the degree of general physical health status and mental health distress. Higher scores indicate higher levels of health. The physical and mental health scores on the 12-Item Short Form Survey (SF-12) are reported as T scores (mean, 50±10, 50 indicates the population mean with a standard deviation of 10), with higher scores indicating better health status.	24 Months
Kansas City Cardiomyopathy Questionnaire (KCCQ)	Quality of Life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ). KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life, in which higher scores reflect better health status. Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary range from 0 to 100, with higher scores indicating a better quality of life and fewer symptoms and physical limitations associated with heart failure.	24 Months
EuroQoL (EQ-5D)	Quality of Life assessed by EuroQoL (EQ-5D) - a standardised instrument for use as a measure of health outcome. Scores on the EuroQol (EQ-5D) visual analogue scale range from 0 (worst imaginable health) to 100 (best imaginable health). Higher scores indicate higher levels of health.	24 Months
Number of Participants With Readmission	Incidence of readmissions	up to 24 months
Number of Participants With TV Reoperations	Number of participants with TV reoperations	up to 24 months
Economic Measures (Inpatient Costs)	Inpatient costs will be measured through the collection of hospital billing.	up to 60 months
Number of Participants With Serious Adverse Events	Safety as measured by frequency of serious adverse events.	24 months
Gait Speed Test	Frailty will be assessed using the Gait Speed Test, which measures the average speed of three 5 meter walks	24 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Canadian Institutes of Health Research (CIHR); Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK); German Society for Thoracic and Cardiovascular Surgery
• Investigators: Principal Investigator: Annetine C. Gelijns, PhD, Icahn School of Medicine at Mount Sinai; Study Chair: Richard Weisel, MD, Toronto General Hospital

Publications and helpful links

General Publications

• Gammie JS, Chu MWA, Falk V, Overbey JR, Moskowitz AJ, Gillinov M, Mack MJ, Voisine P, Krane M, Yerokun B, Bowdish ME, Conradi L, Bolling SF, Miller MA, Taddei-Peters WC, Jeffries NO, Parides MK, Weisel R, Jessup M, Rose EA, Mullen JC, Raymond S, Moquete EG, O'Sullivan K, Marks ME, Iribarne A, Beyersdorf F, Borger MA, Geirsson A, Bagiella E, Hung J, Gelijns AC, O'Gara PT, Ailawadi G; CTSN Investigators. Concomitant Tricuspid Repair in Patients with Degenerative Mitral Regurgitation. N Engl J Med. 2022 Jan 27;386(4):327-339. doi: 10.1056/NEJMoa2115961. Epub 2021 Nov 13.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2016
• Primary Completion (Actual): April 19, 2021
• Study Completion (Actual): April 19, 2021

Study Registration Dates

• First Submitted: January 29, 2016
• First Submitted That Met QC Criteria: February 3, 2016
• First Posted (Estimated): February 5, 2016

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Tricuspid Valve Regurgitation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Tricuspid Valve Insufficiency
• Other Study ID Numbers: GCO 08-1078-0010; 2U01HL088942-07 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No