Heart failure (HF) and moderate-to-severe mitral regurgitation (MR) with residual elevations in left atrial pressure (LAP) after MitraClip may remain symptomatic and experience subsequent HF readmissions. The V-Wave interatrial shunt system is a permanent interatrial septal implant that shunts blood from the left-to-right atrium and serves to continuously unload the left atrium. Although the V-Wave shunt has previously been studied in patients with HF, the safety and feasibility of its deployment at the time of the MitraClip procedure is unknown.
The V-Wave Shunt MitraClip Study (NCT04729933) is an early feasibility study that aims to demonstrate the safety and efficacy of implantation of the V-Wave shunt device at the time of MitraClip procedure. Patients with moderate-to-severe secondary MR with left ventricular ejection fraction 20% to 50% and New York Heart Association functional class III/IV symptoms despite optimal medical therapy, residual mean LAP ≥20 mm Hg after MitraClip, and mean LAP–right atrial pressure difference ≥5 mm Hg are included. The primary safety end point is a composite outcome of all-cause death, stroke, myocardial infarction device embolization, cardiac tamponade, or device-related re-intervention or surgery at 30 days. Patients will be followed up to 5 years. Enrollment is ongoing, with 30-day results expected by the end of 2024.
The V-Wave Shunt Mitraclip Study aims to demonstrate the safety and efficacy of the implantation of the V-Wave interatrial shunt device at the time of index MitraClip placement which may serve as an adjunctive method by which continuous left atrial unloading may be achieved.
Heart failure (HF) affects over 6.2 million adults in the United States. , HF is highly morbid and causes reduced quality of life (QOL), increased likelihood of hospitalization, and high mortality—even with the best available medical and device therapies. , Patients with a reduced left ventricular (LV) systolic ejection fraction (EF) are at particularly high risk of HF symptoms including respiratory distress, which is typically caused by elevated left atrial (LA) pressures, which in turn leads to pulmonary venous congestion and pulmonary edema. Pulmonary congestion accounts for approximately 90% of acute HF hospitalizations, and if not reversed can lead to respiratory failure, cardiogenic shock, cardiac arrhythmia, and death.
Mitral regurgitation (MR) is common in patients with left-sided HF. MR increases LA pressures and exacerbates symptoms of pulmonary congestion. Pathophysiologically, MR may be because of (1) an abnormality of the mitral valve (MV) or its subvalvular apparatus (degenerative MR), or (2) dilatation of the MV annulus as a result of LV or LA enlargement (functional MR). The Cardiovascular Outcomes Assessment of the MitraClip (Abbott, Santa Clara, CA) Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial demonstrated that patients with reduced LVEF and functional MR treated with percutaneous MV repair using MitraClip had reduced risk of hospitalization, improved QOL, and improved survival compared with medical therapy alone.
Despite this, these patients often still have a significant burden of HF, and there remains an unmet need for innovative treatments in patients with reduced LVEF and functional MR after MitraClip. Decompression of the LA could be accomplished by an implanted device that allows left-to-right shunting between the left and right atria. One such percutaneous interatrial shunt is the V-Wave interatrial shunt system (herein referred to as the “V-Wave Shunt”).
The goal of the V-Wave Shunt MitraClip Study is to evaluate the feasibility and safety of implantation of the V-Wave Shunt device in patients with HF with LVEF 20% to 50% who have undergone successful MitraClip placement. Given the obligatory step of interatrial septostomy during the MitraClip procedure, the V-Wave device can subsequently be implanted across the interatrial septostomy site to serve as a permanent interatrial shunt. Early experience with this device has demonstrated its safety in patients with both preserved and reduced LVEF, but patients with significant MR and those receiving MitraClip have been excluded from studies to date. This device therapy may serve as a complementary treatment in patients with HF who remain moderately to severely symptomatic despite management with existing optimal medical therapies.
Methods
The V-Wave Shunt MitraClip Study is a prospective study with the intent to implant the V-Wave shunt device after MitraClip in 10 patients. This is a single-center (Cleveland Clinic, Cleveland, Ohio), investigator-initiated study, designed by the principal investigators and sponsor, V-Wave, Inc., in concordance with regulations set forth by the Food and Drug Administration (FDA). The V-Wave Shunt MitraClip Study has received investigational device exemption status as an early feasibility study by the FDA and is registered at ClinicalTrials.gov under the identifier NCT04729933. The study device will be implanted by a team of 23 operators, all of whom are skilled in structural heart procedures including transseptal puncture and MitraClip placement. The number of patients to be included in the study was decided upon between the investigators and the FDA and was considered to be sufficient to demonstrate early feasibility while potentially identifying any signals of benefit. The primary objective of this study is to demonstrate that implantation of the V-Wave Shunt System immediately after MitraClip placement is feasible and safe, with a secondary objective of assessing for a signal of efficacy.
A complete list of primary and secondary end points is listed in Table 1 . The primary end point of the study will be to demonstrate device safety as measured by the percentage of Treatment Group patients experiencing any device-related major adverse cardiovascular or neurological events (MACNE) during the first 30 days after attempted device placement. MACNE is defined as all-cause death, stroke, myocardial infarction, V-Wave shunt device embolization, cardiac tamponade, or device-related re-intervention or surgery. Patients will be followed for up to 5 years for the assessment of adverse events.
| Primary safety endpoints * |
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| Secondary clinical and laboratory endpoints † |
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| Secondary echocardiographic endpoints † |
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| Secondary device and procedural endpoints † |
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⁎ Composite and individual endpoint assessment at 30 days
† Primary analysis of secondary endpoints will be change from baseline to 12 months
Several efficacy outcomes will be assessed as secondary end points which can be categorized into clinical outcomes, echocardiographic parameters, study device success, and procedural success ( Table 1 ). The goal of including these end points is to detect a signal of efficacy, as the study will not be powered for these outcomes. Outcomes will be compared in individual patients before and after study device placement (paired analyses) and in all patients before compared with after study device placement (where applicable). The primary analysis of these secondary end points will be baseline compared with 12 months; however, secondary analyses for the secondary end points will be evaluated at 1 month, 6 months, 12 months, 2 years, 3 years, and 5 years.
Technical success will be measured at the time of exit from the catheterization lab and is defined as (1) an alive patient with successful delivery and retrieval of the transcatheter V-Wave delivery system, (2) deployment and correct positioning of the single intended device, and (3) no need for additional emergency surgery or re-intervention related to either the device or the access procedure. Device success will be measured at 30 days and all post-procedural intervals. It is defined as alive and stroke-free, with original intended device in place and no additional surgical or interventional procedures related to access or the device. This end point will also include intended hemodynamic performance of the device including patent device with ratio of total pulmonary blood flow (Qp) to total systemic blood flow (Qs) <1.5 if captured on echocardiogram. Finally, there should be no detected device or para-device complications such as device leak, migration, erosion, detachment, fracture, systemic or pulmonary embolization, hemolysis, or endocarditis.
Procedural success will be measured at 30 days and is defined as device success and no device or procedure-related serious adverse events including life-threatening bleeding (defined as requiring transfusion of >4 units of packed red blood cells), acute kidney injury (stage 2 or 3, including renal replacement therapy), major vascular complications or tamponade requiring intervention, myocardial infarction or coronary ischemia requiring percutaneous coronary intervention or coronary artery bypass grafting, severe hypotension, HF requiring intravenous pressors or invasive/mechanical HF treatment, or respiratory failure requiring prolonged intubation for ≥48 hours, related to the study device or procedure.
The V-Wave interatrial shunt system consists of 2 major components: (1) V-Wave interatrial shunt, part number 51140125, and (2) V-Wave delivery system, part number 85014155 ( Figure 1 ). The delivery system is introduced through a 14-Fr inner diameter delivery sheath placed in the LA after a standard femoral venous access transseptal cardiac catheterization procedure. In this case, the MitraClip procedure will be performed, and the existing transseptal communication created by the MitraClip procedure will be used for V-Wave shunt placement. Specifically, after completion of the MitraClip procedure with a satisfactory result and confirmation the patient satisfies all inclusion and exclusion criteria, wire access will be maintained in the LA, the MitraClip delivery system and sheath removed, and replaced with a 20-Fr sheath using the same venous access point utilized for the MitraClip procedure. Then, the 14-Fr V-Wave delivery sheath will be introduced into the LA, and V-Wave device deployed in a standard fashion.
The V-Wave Shunt is constructed on an hourglass-shaped, self-expanding Nitinol frame, with expanded polytetrafluoroethylene encapsulation to block tissue ingrowth. The shunt is implanted across the fossa ovalis of the interatrial septum with a total length of 12 mm. The external diameter at the right and LA ends are 11 and 14 mm, respectively. The shunt created is 5.1 mm in diameter. The implant is designed for single use and is sterilized using ethylene oxide.
The V-Wave delivery system includes a delivery catheter and loading tools. The loading tools are used to compress the shunt for attachment to the distal end of the delivery catheter and for loading the shunt/catheter into the delivery sheath. The delivery sheath is a commercially available Cook Medical (Bloomington, Indiana) 14 Fr Mullins introducer sheath (Part Number RCFW-14.0-38-85-RB). The delivery catheter includes a handle to control the release of the shunt, a flushing port, and a safety clip to prevent unintended release of the shunt. The implanting physician (herein referred to as the “implanter-investigator”) will be an interventional cardiologist highly experienced in ultrasound-guided transseptal catheterization and structural heart disease. Implanter investigators will be trained in the proper use of the V-Wave interatrial shunt system, first on a benchtop model and then proctored during the first 3 cases at a minimum, per the protocol requirements.
Eligible subjects will be aged 18 years or older and must meet criteria for commercial MitraClip placement for secondary MR as has been described elsewhere. These criteria include patients with moderate-to-severe secondary MR at least 3 to 4+ because of either ischemic or non-ischemic cardiomyopathy with LVEF 20% to 50% and New York Heart Association (NYHA) functional class III/IV symptoms despite maximally tolerated guideline-directed medical therapy. Patients should meet anatomic eligibility criteria for MitraClip placement with subsequent successful device therapy defined as residual MR<2+.
Patients will be screened for Primary Exclusion Criteria (PEC) which include severe pulmonary hypertension (PH), moderate-to-severe right ventricular dysfunction, and severe (3+ to 4+) tricuspid or pulmonic regurgitation ( Table 2 ). PEC will be assessed at the screening visit, whereas final exclusion criteria (FEC) will be assessed at the time of cardiac catheterization (study intervention visit) before V-Wave shunt device placement.
