TEER for Severe DMR of Low to Intermediate Surgery Risk

Official title

The Efficacy and Safety of TEER for Severe DMR Patients of Low to Intermediate Surgery Risk (TESLA-R)--a Multi-center, Prospective Cohort Study

Overview

To investigate the efficacy and safety of transcatheter mitral valve edge-to-edge repair (TEER) for severe degenerative mitral regurgitation (DMR) patients of low to intermediate surgery risk.

Detailed description

This is a proposed multicentre, prospective cohort study to enrol and follow up severe DMR patients of low to intermediate surgery risk who underwent TEER, and surgical historical controls. The primary efficacy endpoints are all-cause death and cumulative composite event rate of worsening heart failure at 24 months postoperatively, and the primary safety endpoints are death, secondary surgery, and various complications at 30 days postoperatively. The study aims to investigate the efficacy and safety of TEER in surgical low-intermediate-risk patients with severe DMR, and to inform the subsequent clinical application.

Interventions

• Diagnostic test ultrasonic cardiography (UCG)
  Trans-thoracic echocardiography (TTE) is performed in the resting position. Trans-esophageal echocardiography (TEE) is performed under surface anaesthesia with bupivacaine or intravenous anaesthesia. We comprehensively assess the severity of mitral regurgitation according to American Society of Echocardiography (ASE) guideline.
• Procedure TEER
  Two commercial cliping systems are available for clinical use: the G3 MitraclipTM and the G4 MitraclipTM (Abbott), DragonflyTM (Dejin), which will be introduced to the Chinese market in 2024, with the specific choice determined by the operator. The patient receives general anaesthesia (intravenous and endotracheal). The operator performs the procedure according to the recommended surgical steps in the product manual, guided by X-ray and trans-esophageal echocardiography. Postoperative MR ≤2+ is

Primary outcome measures

• cumulative composite event rate of the main adverse events [Time frame: time of operation to 30 days after operation]
• cumulative composite event rate of all-cause death and worsening heart failure [Time frame: time of operation to 24 months after operation]

Eligibility criteria

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) effective regurgitant orifice area (EROA) ≥0.3cm\^2; 2) regurgitant volume (RVol) ≥45ml; 3) regurgitant fraction (RF) ≥40%.
• symptomatic heart failure ( New York Heart Association (NYHA) class II-IV ), or asymptomatic heart failure with left ventricular end systolic dimension (LVESd) ≥40mm or ejection fraction (EF) ≤60%, or new-onset atrial fibrillation, or resting pulmonary artery systolic pressure (PASP) >50mmHg.
• The patient with American Association of Thoracic Surgeons Score (STS) <8 has surgical indications evaluated by cardiac team.
• 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) severe calcification presents in the flap leaflet clamping area; 3) mitral valve cleft; 4) multiple regurgitant flow, especially in the internal and external union junction area; 5) Barlow disease; 6) leaflet length <7mm; 7) flail gap >10mm; 8) flail width >15mm.
• severe cardiac insufficiency ( NYHA class IV or lefr ventricular ejection fraction (LVEF) <20% ), end-stage heart failure status ( American College of Cardiology/American Heart Association (ACC/AHA) Stage D), relying on circulation aids or waiting for heart transplantation.
• proposed implantation of heart failure device such as cardiac resynchronization therapy/cardiac resynchronization therapy defibrillator (CRT/CRT-D) or cardiac contractility modulation (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. pulmonary arterial hypertension (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 systemic lupus erythematosus (SLE).
• amyloidosis.
• severe infections, septicaemia.
• severe hepatic insufficiency, e.g. acute severe hepatitis, decompensated cirrhosis ( Child-Pugh class C)
• severe renal insufficiency ( chronic kidney disease (CKD) stage 5: estimated glomerular filtration rate (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 international normalized ratio (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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

China · 1 center

• Sun Yat-sen Memorial Hospital of Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT06162780 · SYSKY-2023-1019-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗