TEER for Low-intermediate Surgery Risk DMR

Study Overview
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Brief Summary
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To investigate the efficacy and safety of TEER for severe degenerative mitral regurgitation patients of low to intermediate surgery risk.

Detailed Description
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In the multi-center and prospective cohort study, we will include and follow up 268 severe degenerative mitral regurgitation patients of low-intermediate surgical risk,including 134 patients who refuse surgery but undergo TEER, and 134 matched patients who undergo surgical procedures.The primary effectiveness endpoint is the cumulative composite event rate of all-cause death and worsening heart failure at 24 months postoperatively. The primary safety endpoints are death, secondary surgery, and various complications at 30 days postoperatively.We aim to investigate the efficacy and safety of TEER in these patients and to provide a basis for subsequent clinical practice.

Official Title
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The Efficacy and Safety of TEer for Severe Degenerative Mitral Regurgitation Patients of Low to intermediAte Surgery Risk (TESLA-R) --A Multi-center, Prospective Cohort Study

Conditions
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Mitral Regurgitation

Intervention / Treatment
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* Diagnostic Test: ultrasonic cardiography
* Procedure: Transcatheter mitral valve Edge-to-Edge Repair


Participation Criteria
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Eligibility Criteria
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TEER group Inclusion Criteria: the patient fully meets the following criteria. age ≥ 18 years old DMR ≥ grade 3+ according to UCG integrative approach, referring to the following quantitative indicators: 1) EROA ≥0.3cm^2; 2) RVol ≥45ml; 3) RF ≥40% symptomatic heart failure ( NYHA class II-IV ), or asymptomatic heart failure with LVESd ≥40mm or EF ≤60%, or new-onset atrial fibrillation, or resting PASP >50mmHg The patient with STS score <8 has surgical indications evaluated by cardiac team, but he/she refuses surgery. The patient has signed an informed consent form and agreed to regular follow-up for at least 1 year. Exclusion Criteria: the patient meets any of the following criteria. active infective endocarditis especially occurring in the mitral valve area, or mitral valve perforation rheumatic mitral valve disease, mitral stenosis or mitral valve orifice area < 4mm^2 combined valve lesions requiring surgery, e.g. severe tricuspid regurgitation or aortic valve disease the present of tumour, thrombus or redundant organisms in the heart chambers inability to tolerate intraoperative or postoperative antithrombotic (anticoagulant or antiplate) therapy acute DMR, e.g. DMR caused by acute papillary muscle rupture Due to the presence of certain anatomical conditions, patient has a low success rate for TEER assessed by the operator and is not appropriate for enrolment. The conditions include but are not limited to the followings: 1) the venous approach is not suitable for operation, such as thrombus in the approach and small vein diameter; 2) the septum is not suitable for puncture, such as the location of the septum penetration is less than 4cm from the mitral annular plane; 3) severe calcification presents in the flap leaflet clamping area; 4) mitral valve cleft; 5) multiple regurgitant flow, especially in the internal and external union junction area; 6) Barlow disease; 7) leaflet length <7mm; 8) flail gap >10mm; 9) flail width >15mm. severe cardiac insufficiency ( NYHA class IV or LVEF <20% ), end-stage heart failure status ( ACC/AHA Stage D), relying on circulation aids or waiting for heart transplantation proposed implantation of heart failure device such as CRT/CRT-D or CCM untreated severe coronary artery stenosis requiring coronary revascularization, or other cardiac macrovascular disease requiring surgery hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or structural heart disease leading to heart failure other than dilated heart disease severe pulmonary hypertension ( PASP >70 mmHg), or pulmonary hypertension associated with no-left heart disease, e.g. PAH etc. acute myocardial infarction within 4 weeks before operation acute cerebrovascular accident within 30 days before operation acute peptic ulcer or upper gastrointestinal bleeding within 3 months before operation uncontrolled hyperthyroidism uncontrolled autoimmune connective tissue diseases especially Behcet s disease and SLE amyloidosis severe infections, septicaemia severe hepatic insufficiency, e.g. acute severe hepatitis, decompensated cirrhosis ( Child-Pugh class C) severe renal insufficiency ( CKD stage 5: eGFR < 15 ml/min or dialysis) hypotensive state, shock ( systolic blood pressure < 90mmHg or mean arterial pressure <70 mmHg with tissue hypoperfusion and urine output < 30 ml/h) uncontrolled diseases of the haematological system: acute gastrointestinal bleeding, intracranial haemorrhage or haemorrhage from other organs, acute pulmonary embolism or deep vein thrombosis, congenital or acquired haemorrhagic disease such as haemophilia, anaphylactic purpura and acute leukaemia, severe abnormalities in haematological parameters such as platelet count <20*10^9/l and INR >3 contraindication for TEE, e.g. oesophageal constriction, oesophageal tumour, oesophageal fistula, oesophageal varices, cervical vertebral instability, etc. contraindication for intravenous anaesthesia, e.g. allergy to anaesthetics pregnancy or breastfeeding The patient does not sign an informed consent form. expected survival less than 1 year The patient with poor compliance is not thought to complete follow-up visits. The patient is participating in an experimental drug or other device study with an incomplete primary endpoint, or the patient is participating in an unfinished experimental drug or other device study that would clinically interfere with our study endpoints. Due to other reasons the patient is not suitable for enrollment assessed by the researcher. surgery group Inclusion Criteria: the patient fully meets the following criteria. DMR of ≥grade 3+ , having surgical indications evaluated by cardiac team, low to intermediate surgery risk The patient agrees to surgery. The patient has signed an informed consent form and agreed to regular follow-up for at least 1 year. Exclusion Criteria: the patient meets any of the following criteria. high surgery risk or contraindication for surgery The patient does not sign an informed consent form. The patient with poor compliance can not complete follow-up visits. Due to other reasons the patient is not suitable for enrollment assessed by the researcher.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TEER group<br>Severe degenerative mitral regurgitation patients of low to intermediate surgery risk who refused surgery and underwent TEER. | Diagnostic Test: ultrasonic cardiography<br>* Trans-thoracic echocardiography is performed in the resting position. Trans-esophageal echocardiography is performed under surface anaesthesia with bupivacaine or intravenous anaesthesia. We comprehensively assess the severity of mitral regurgitation according to ASE guideline.<br>Procedure: Transcatheter mitral valve Edge-to-Edge Repair<br>* There are two commercial systems including Mitraclip and Dragonfly for clinical use. The patient who receives general anaesthesia undergoes operation guided by X-ray and trans-esophageal echocardiography, according to the recommended surgical procedure. MR success is defined as DMR ≤ grade 2+ after TEER. After crossing the atrial septum during the operation, full dose heparin was given for anticoagulation. Post-intervention antithrombotic therapy was used as indicated. Anticoagulation was chosen if the patient has an indication for anticoagulation, otherwise aspirin was prescribed.<br>|
| surgery group<br>Severe degenerative mitral regurgitation patients of low to intermediate surgery risk who underwent surgical procedures. | Diagnostic Test: ultrasonic cardiography<br>* Trans-thoracic echocardiography is performed in the resting position. Trans-esophageal echocardiography is performed under surface anaesthesia with bupivacaine or intravenous anaesthesia. We comprehensively assess the severity of mitral regurgitation according to ASE guideline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cumulative composite event rate of the main adverse events | The main adverse events: death, acute myocardial infarction, requiring secondary therapy for valve treatment failure, requiring cardiovascular emergency surgery for main complications, stroke, kidney failure, deep infection, >48 hours mechanical ventilation, new-onset atrial fibrillation, deep vein thrombosis, pulmonary embolism, sepsis, haemorrhage, blood transfusion >2U | time of operation to 30 days after operation | 
| cumulative composite event rate of all-cause death and worsening heart failure | all-cause mortality: deaths from all causes including cardiovascular and non-cardiovascular deaths. worsening heart failure: heart failure rehospitalization, worsening heart failure needing emergency room visit, NYHA classification increased by one, ineffective escalation of medication on outpatient service, receiving intravenous diuretic therapy on outpatient or emergency service. | time of operation to 24 months after operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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degenerative mitral regurgitation, transcatheter mitral valve edge-to-edge repair, surgery risk