Implantation of a Permanent Interatrial Shunt to Reduce Left Atrial Filling Pressures Following MitraClip
Implantation of a Permanent Interatrial Shunt to Reduce Left Atrial Filling Pressures Following MitraClip
This is an investigator initiated, prospective study to demonstrate the safety and
 feasibility of implantation of the V-Wave Interatrial Shunt System (herein called the "V-Wave
 Shunt" in patients immediately following percutaneous mitral valve repair using the MitraClip
 system.
The V-Wave Shunt is a device placed across the interatrial septum (IAS) by cardiac
 catheterization which allows for the transfer of blood from the left atrium (LA) to right
 atrium (RA). The intended effect is to reduce excessive left-sided cardiac filling pressures
 in patients with advanced heart failure (HF) and thus improve symptoms related to pulmonary
 congestion. All patients in the study must meet all anatomic and clinical eligibility in the
 FDA approved indications for use of the MitraClip in functional mitral regurgitation (MR).
 All patients must have persistence of New York Heart Association (NYHA) class III or
 ambulatory class IV HF symptoms despite maximally tolerated guideline directed medical
 therapy (GDMT) as assessed by a Cardiologist specialist in advanced heart failure (HF). All
 patients will have reduced left ventricular (LV) ejection fraction (EF) ≥ 20% and ≤ 50% and
 at least moderate to severe 3-4+ MR with a functional or combined functional and degenerative
 mechanism. Despite MitraClip treatment and maximum GDMT, these patients are at high risk for
 recurrent HF events and readmission, and thus there is an unmet need for further therapies to
 improve outcomes in this patient population.

 The existing transseptal puncture used for MitraClip placement will be used to place the
 V-Wave Shunt device after MitraClip placement.
Inclusion Criteria:

 1. All patients must meet clinical and anatomic eligibility for commercial placement of
 MitraClip for functional MR, as specified by the MitraClip Instructions for Use (IFU).

 a. Clinical eligibility for MitraClip: i. Symptomatic secondary MR (moderate-severe [3+ or
 4+] or greater) due to ischemic or non-ischemic cardiomyopathy ii. NYHA functional class
 III, or ambulatory IV iii. Maximization of GDMT as directed by the "Heart Team", including
 an interventional cardiologist (implanting physician), heart failure cardiologist, and
 cardiothoracic surgeon. This includes adequate treatment for systolic HF (LV dysfunction),
 rhythm disorders, and coronary disease, if applicable

 1. An inhibitor of the reninangiotensin system (RAS inhibitor), including an angiotensin
 converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) or angiotensin
 receptor-neprilysin inhibitor (ARNI) and a beta-blocker (BB)

 2. Other medications recommended for selected populations, e.g., mineralocorticoid
 receptor antagonist (MRA) or nitrates/hydralazine should be used in appropriate
 patients, according to the published guidelines.

 3. Patient has been on stable HF medications as determined by the investigator, for at
 least 1 month, with the exception of diuretic therapy. Stable is defined as no more
 than a 100% increase or 50% decrease in dose within these periods.

 4. Drug intolerance, contraindications, or lack of indications must be attested to by the
 investigator.

 5. Receiving Class I recommended cardiac rhythm management device therapy.

 1. If indicated by class I guidelines, cardiac resynchronization therapy (CRT),
 implanted cardioverter-defibrillator (ICD) or a pacemaker should be implanted at
 least 3 months prior to device implantation

 2. These criteria may be waived if a patient is clinically contraindicated for these
 therapies or refuses them and must be attested to by the investigator.

 iv. At least one hospitalization for heart failure in last year OR corrected BNP ≥ 300
 pg/mL or corrected NTproBNP ≥ 1500 pg/mL v. Heart team has determined that mitral valve
 (MV) surgery will not be offered as a treatment option b. Anatomic eligibility for
 MitraClip: i. LVEF ≥ 20% and ≤ 50% ii. LV end-systolic dimension ≤ 70 mm iii. MV orifice
 area > 4.0 cm2 by TEE iv. Minimal calcification in the grasping area v. No leaflet cleft in
 the grasping area vi. In patients with a degenerative component to MR, the following
 additional criteria must be met:

 1. Flail width <15 mm

 2. Flail gap <10 mm vii. The primary regurgitant jet is non-commissural, and in the
 opinion of the implanting investigator can be successfully be treated by the MitraClip
 (if a secondary jet exists, it must be considered clinically insignificant) viii.
 Transseptal catheterization and femoral vein access is feasible per investigator 2.
 Provide written informed consent for study participation and be willing and able to
 comply with the required tests, treatment instructions and follow-up visits.

 Exclusion Criteria:

 Preliminary Exclusion Criteria (PEC) - to assessed by the Preliminary Screen at the
 baseline visit:

 1. Severe pulmonary hypertension, defined as RV systolic pressure or PA systolic pressure
 > 70 mmHg, or PVR > 4 Woods units, measured by any modality (TTE, TEE, cardiac MRI, or
 pulmonary artery catheterization [if data available]).

 2. Moderate or severe RV dysfunction defined as TAPSE <12mm or RVFAC ≤25% as assessed on
 Baseline TTE, or qualitative assessment of severe RV dysfunction on TTE, TEE, or
 cardiac MRI.

 3. Untreated severe (3+ to 4+) tricuspid or pulmonary regurgitation.

 4. Untreated clinically significant coronary disease requiring revascularization

 5. Coronary artery bypass grafting, percutaneous coronary intervention, transcatheter
 aortic valve implantation, or CRT-D implantation within 30 days

 6. Aortic or tricuspid valve requiring surgery or transcatheter intervention

 7. COPD requiring continuous home oxygen therapy or chronic outpatient steroid use

 8. Cerebrovascular accident within prior 30 days

 9. Known severe symptomatic carotid stenosis

 10. Carotid surgery or stenting within prior 30 days

 11. ACC/AHA Stage D heart failure

 12. Presence of any of the following:

 1. Hypertrophy cardiomyopathy, restrictive cardiomyopathy, constrictive
 pericarditis, or any other structural heart disease causing heart failure other
 than dilated cardiomyopathy of either ischemic or non-ischemic etiology

 2. Infiltrative cardiomyopathy (e.g. amyloidosis, hemochromatosis, sarcoidosis)

 13. Leaflet anatomy which may preclude MitraClip implantation

 14. Hemodynamic instability defined as systolic pressure < 90 mmHg with or without
 afterload reduction, cardiogenic shock or the need for inotropic support or
 intra-aortic balloon pump or other hemodynamic support device.

 15. Need for surgery within 12 months

 16. Life expectancy < 1 year due to non-cardiac conditions

 17. Status 1 for cardiac transplant or history of cardiac transplant

 18. Modified Rankin score ≥ 4 for disability

 19. Prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve,
 or any prior transcatheter mitral valve procedure

 20. Echocardiographic evidence of intracardiac mass, thrombus, or vegetation

 21. Active endocarditis or active rheumatic heart disease or leaflets degenerated from
 rheumatic disease (i.e., noncompliant, perforated)

 22. Active infection requiring antibiotic therapy

 23. TEE is contraindicated or high risk

 24. Pregnant or planning pregnancy within 12 months

 25. Known hypersensitivity or contraindication to procedural medications that cannot be
 adequately treated

 26. Known allergy to nickel.

 27. Patient is otherwise not appropriate for the study as determined by the investigator
 or the Eligibility Committee, for which the reasons must be documented.

 28. Patient belongs to a vulnerable population per investigator's judgment or patient has
 any kind of disorder that compromises his/her ability to give written informed consent
 and/or to comply with study procedures.

 Final Exclusion Criteria (FEC) - Assessed by the Final Screening, performed at time of
 cardiac catheterization prior to device placement (Study Intervention Visit)

 29. Presence of severe pulmonary hypertension assessed by invasive hemodynamic measurement
 with pulmonary artery catheterization prior to MitraClip placement, defined as PA
 systolic pressure > 70 mmHg or PVR > 4 Woods units.

 30. Anatomical anomaly on TEE that precludes implantation of the study device across the
 interatrial communication created by the MitraClip procedure, including:

 1. A posterior rim between the septum secundum and aorta (i.e. aortic rim) of < 5
 mm.

 2. Atrial septal aneurysm defined as ≥ 10 mm of phasic septal excursion into either
 atrium or a sum total excursion of ≥ 15 mm during the cardiorespiratory cycle,
 with a base of ≥ 15 mm.

 31. Moderate or worse MR ≥2+ at the end of MitraClip treatment (i.e. MR must be <2+ by
 TTE, TEE, invasive hemodynamics, or left ventriculography)

 32. Key hemodynamic exclusions after MitraClip treatment:

 1. Mean LAP ≤ 20 mmHg following final result from MitraClip placement (i.e. mean LAP
 must be elevated > 20 mmHg after completion of MitraClip).

 2. Difference between mean LAP and mean RAP < 5mmHg after MitraClip placement (i.e.
 difference between LAP - RAP must be ≥ 5 mmHg).

 3. If the patient meets these hemodynamic exclusion criteria and mean arterial
 pressure (MAP) is < 90 mmHg, the MAP may be increased to ≥ 90 mmHg and repeat
 pressure measurements obtained in order to evaluate eligibility.

 i. IV fluids and medications may be given to support MAP to a goal ≥ 90 mmHg if
 necessary.

 33. Patient is otherwise not appropriate for study as determined by the Investigator.