Heart Failure - NYHA II - IV, Mitral Regurgitation Functional
Conditions
Keywords
secondary mitral regurgitation, exercise-induced severe mitral regurgitation, dynamic mitral regurgitation
Brief summary
The goal of this clinical trial is to learn whether mitral valve transcatheter edge-to-edge repair (TEER) in addition to guideline-directed medical therapy (GDMT) can improve clinical outcomes and symptoms in heart failure patients with non-severe secondary mitral regurgitation (SMR) at rest and exercise-induced severe SMR. The main questions it aims to answer are: * Does mitral valve TEER in addition to GDMT lead to better overall clinical outcomes than GDMT alone in patients with heart failure and exercise-induced severe SMR? * Does mitral valve TEER reduce the risk of death, heart failure hospitalization, or worsening SMR during 12 months of follow-up compared with GDMT alone? * Does mitral valve TEER improve patients' quality of life compared with GDMT alone? Participants will: * Undergo screening assessments to confirm eligibility for the study. * Be randomly assigned to receive either GDMT alone or GDMT plus mitral valve TEER. * Attend follow-up visits at approximately 3 time points during a 12-month follow-up period. * Undergo clinical evaluations that are routinely performed in patients with heart failure and SMR, including assessment of symptoms, functional status, and cardiac function. The patients' echocardiographic data will undergo an additional centralized assessment by an independent Core Laboratory.
Interventions
Participants receive guideline-directed medical therapy (GDMT) for heart failure and secondary mitral regurgitation (SMR) according to current clinical practice guidelines. Medical treatment may include optimized pharmacological therapy such as beta-blockers, ACE inhibitors/ARBs/ARNI, mineralocorticoid receptor antagonists, diuretics, SGLT2-inhibitors and other indicated medications. Treatment is adjusted based on clinical status and treating physician judgment.
PROCEDUREMitral valve TEER
Participants receive guideline-directed medical therapy (GDMT) for heart failure and secondary mitral regurgitation (SMR) according to current clinical practice guidelines in combination with TEER of the mitral valve using the PASCAL Precision system (Edwards Lifesciences Sàrl). The procedure is performed via a minimally invasive transcatheter approach through femoral venous access to reduce SMR. Guideline-directed medical therapy is continued and optimized throughout follow-up according to standard of care.
Sponsors
Jena University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Mild-to-moderate (1+/2+) SMR at rest * Exacerbation of SMR to exercise-induced severe (3+/4+) SMR defined by at least one of the following: * 40 mm\^2 EROA (30 mm\^2 under low-flow condition) or * regurgitant volume ≥60 mL (45 mL under low-flow condition) or * regurgitant fraction ≥40% or * increase by 13 mm\^2 EROA from rest to exercise * Increase in natriuretic peptides defined as NT-proBNP: * \>250 pg/ml (Sinus rhythm) or * \>600 pg/ml (Atrial fibrillation) or * HF hospitalization within 12 months prior to screening (defined as HF listed as the major reason for hospitalization) * NYHA class II-IV * Stable HF medication regimen (GDMT) for at least 30 days prior to index procedure * Patient deemed appropriate candidate for TEER by the local multidisciplinary heart team * Age ≥ 18 years old * Written Informed consent
Exclusion criteria
* Hospitalization in past three months due to myocardial infarction, coronary artery bypass graft surgery, and/or unstable angina * LVEDD \>70 mm * LVEF \<20% * Evidence of transient ischemic attack or stroke within three months prior to intervention * Percutaneous coronary intervention in the last 30 days * Subjects expected to require any cardiac surgery, including surgery for coronary artery disease or for pulmonic, aortic, or tricuspid valve disease within one year * Presence of primary renal dysfunction or significantly compromised renal function (eGFR \<30 ml/min) * Severe right ventricular failure * Severe aortic stenosis (aortic valve area \<1.0 cm\^2) or aortic regurgitation * Hemodynamic instability requiring inotropic support or mechanical heart circulatory support * Presence of a mechanical mitral heart valve, mitral bioprosthetic valve or mitral annuloplasty ring, indication for cardiac resynchronization therapy * Echocardiographic evidence of intracardiac mass, thrombus, or vegetation * Active endocarditis or infections requiring current antibiotic therapy * Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or any other structural heart disease causing HF other than SMR * Inability to exercise * Pregnancy or planning pregnancy within next12 months * Life expectancy \<12 months (judgement of investigator) * Anticipated need of left ventricular assist device within next 12 months * Participation in another interventional clinical trial (primary endpoint not yet reached) during this trial or within 30 days prior to enrolment into this trial * Previous participation in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Four-step hierarchical composite primary endpoint; win ratio based on the following parameters: time to all-cause mortality at 12 months, time to first HF hospitalization, SMR progression (3+/4+) at rest, change in KCCQ score from baseline to 12 months. | 12 months | The primary outcome is a single aggregated, unitless win ratio based on a four-step hierarchical composite primary endpoint at 12 months. Each patient in the GDMT+mitral valve TEER group will be compared with each patient in the GDMT group with respect to the following parameters in the following order: 1. time to all-cause mortality, days 2. time to first heart failure hospitalization, days 3. secondary mitral regurgitation progression (3+/4+) at rest and 4. change in KCCQ score from baseline to 12 months, where higher improvement or less deterioration wins; differences between patients less than 5 points are treated as ties (i.e. a between-patient threshold of 5 pts., KCCQ-values range from 0 to 100, higher values indicating better health). For each pairwise comparison, the first non-tied component determines a win for one group or a tie. The win ratio is the number of wins in the GDMT+ mitral valve TEER group divided by the number of wins in the GDMT group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with cardiovascular death | 12 months | Death due to cardiovascular causes during follow-up. |
| Number of participants with heart failure hospitalization | 12 months | Hospitalization due to worsening heart failure requiring inpatient treatment. |
| Number of participants with myocardial infarction | 12 months | Occurrence of myocardial infarction during follow-up. |
| Number of participants with stroke | 12 months | Occurrence of ischemic or hemorrhagic stroke during follow-up. |
| Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score | Baseline, 1, 6, and 12 months | Health-related quality of life assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ): scores range from 0 to 100, with higher scores indicating better health status. |
| Change from baseline in 36-Item Short Form Survey (SF-36) score | Baseline, 1, 6, and 12 months | General health-related quality of life assessed using the SF-36 questionnaire, including physical and mental component summary scores. |
| Number of participants requiring mitral valve surgery | 12 months | Occurrence of surgical mitral valve intervention during follow-up. |
| Change from baseline in secondary mitral regurgitation severity grade according to the American Society of Echocardiography (ASE) criteria at rest | Baseline, 1, 6, and 12 months | Secondary mitral regurgitation severity will be assessed at rest by transthoracic echocardiography according to the American Society of Echocardiography (ASE) criteria using a 4-grade scale: Grade 1 (mild), Grade 2 (moderate), Grade 3 (moderate-to-severe), and Grade 4 (severe). Severity grading will be based on an integrated assessment of echocardiographic parameters, including effective regurgitant orifice area (EROA), regurgitant volume (RVol), and regurgitant fraction (RF). |
| Change from baseline in left ventricular end-systolic volume index (LVESVi) | Baseline, 1, 6, and 12 months | Left ventricular end-systolic volume index measured by echocardiography. |
| Change from baseline in left ventricular end-diastolic volume index (LVEDVi) | Baseline, 1, 6, and 12 months | Left ventricular end-diastolic volume index measured by echocardiography. |
| Change from baseline in pulmonary artery systolic pressure (SPAP) | Baseline, 1, 6, and 12 months | Pulmonary artery systolic pressure assessed by echocardiography. |
| Change from baseline in New York Heart Association (NYHA) functional class | Baseline, 1, 6, and 12 months | Heart failure functional status assessed using NYHA classification. |
| Change from baseline in six-minute walk test (6MWT) distance | Baseline, 1, 6, and 12 months | Exercise capacity assessed using the six-minute walk test. |
| Change from baseline in NT-proBNP (N-terminal pro Brain natriuretic peptide, pg/ml) (alternatively calculated from BNP, Brain natriuretic peptide, pg/ml) | Baseline, 1, 6, and 12 months | Heart failure biomarkers measured in blood samples. |
Countries
Germany
Contacts
CONTACTChristian Schulze, Prof. Dr.
CONTACTMaximilian Spieker, PD Dr.
STUDY_DIRECTORChristian Schulze, Prof. Dr.
University Hospital Jena
STUDY_DIRECTORMaximilian Spieker, PD Dr.
Heinrich-Heine University, Duesseldorf
Outcome results
None listed