Early Feasibility Study - Transcatheter Atrial Shunt System

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate initial clinical safety, device functionality and effectiveness of the Edwards Transcatheter Atrial Shunt System.

Detailed Description
-----------------
The early feasibility study of the Edwards Transcatheter Atrial Shunt System is a multi-center, prospective, early feasibility study to evaluate initial clinical safety, device functionality, and effectiveness of the Edwards Transcatheter Atrial Shunt System.

Official Title
-----------------
EArLy FeasibiLity Study Of the EdWards Transcatheter Atrial Shunt System (ALt FLOW US)

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Device: Transcatheter Atrial Shunt System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed and dated IRB approved study consent form prior to study related procedures ≥ 18 years old Chronic symptomatic Heart Failure (HF) documented by the following: NYHA class II with a history of NYHA class > II; NYHA class III; or ambulatory NYHA class IV AND ≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV) or intensification of oral diuresis for HF in a healthcare facility (emergency department/acute care facility) within the 12 months prior to study entry; OR an NT-pro BNP value > 150 pg./ml in normal sinus rhythm, > 450 pg./ml in atrial fibrillation, or a BNP value > 50 pg./ml in normal sinus rhythm, > 150 pg./ml in atrial fibrillation within the past 6 months prior to study entry. In the judgment of the investigator, subject is on stable Guideline Directed Medical Therapy (GDMT) for heart failure and management of potential comorbidities according to current ACCF/AHA Guidelines and that is expected to be maintained without change for 3 months At rest: elevated LAP or PCWP pressure of > 15 mmHg and LAP (or PCWP) exceeds right atrial pressure (RAP) by > 5 mmHg AND/OR during supine ergometer exercise stress test, as measured at end-expiration, elevated LA (or PCWP) pressure of > 25 mmHg and LA (or PCWP) exceeds right atrial pressure (RAP) by > 10 mmHg Willing to attend study follow-up assessments for up to 5 years Inclusion Criteria for Cohort B, Heart Failure with Pulmonary Vascular Disease only: Pulmonary Vascular Resistance (PVR) > 3.0 and ≤ 8.0 Wood Units at rest Mean Pulmonary Artery Pressure (mPAP) ≥ 25 mmHg at rest AND If baseline PVR is > 4.0, must show successful reversibility of PH under a resting Sodium Nitroprusside* challenge where success is defined as a lowering of the PVR to a level ≤ 4.0 Wood Units while maintaining a Systolic Blood Pressure ≥ 90 mmHg. Equivalent vasodilator agent (e.g., nitric oxide) may be used as deemed appropriate per hospital practice Exclusion Criteria: Severe heart failure defined as one or more of the below: ACC/AHA/ESC Stage D heart failure, non-ambulatory NYHA Class IV HF If BMI < 30, Cardiac index < 2.0 L/min/m2 If BMI ≥ 30, cardiac index < 1.8 L/min/m2 Inotropic infusion (continuous or intermittent) within the past 6 months Patient is on the cardiac transplant waiting list LVEF < 20% Presence of significant valve disease defined by the site cardiologist as: Mitral valve regurgitation defined as grade > 3+ MR or > moderate MS Tricuspid valve regurgitation defined as grade > 2+ TR Aortic valve disease defined as > 2+ AR or > moderate AS MI and/or any therapeutic invasive, non-valvular cardiac procedure within past 3 months or current indication for coronary revascularization Surgical valve repair or replacement within the past 12 months; Transcatheter valve repair or replacement within the past 6 months. Cardiac Resynchronization Therapy initiated, stroke or transient ischemic attack (TIA) within the past 6 months Hemodynamic instability within 30 days of scheduled implant procedure Patient requiring surgery under general anesthesia for any reason within 30 days of scheduled implant procedure Clinically diagnosed hypertrophic obstructive cardiomyopathy, constrictive pericarditis or other infiltrative cardiomyopathy (eg, hemochromatosis, sarcoidosis) Has renal insufficiency as determined by creatinine (S-Cr) level > 2.5 mg/dL or estimated-GFR < 25ml/min/1.73 m2 by CKD-Epi equation; or currently requiring dialysis Significant hepatic impairment defined as 3× upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase Performance of the 6 minute walk test with a distance <50m OR >600m Subject is contraindicated to receive either dual antiplatelet therapy or warfarin (analogue); or has a documented coagulopathy Known hypersensitivity to anticoagulation therapy or contrast agent, which cannot be adequately medicated Known hypersensitivity to Nickel and/or Tantalum In the judgment of the investigator, life expectancy <12 months for noncardiovascular reasons In the opinion of the investigator, the subject is not an appropriate candidate for the study Anatomy (including implantable devices) that is not compatible with the Edwards Transcatheter Atrial Shunt System Active endocarditis or infection within 3 months of scheduled implant procedure Currently participating (e.g., undergoing trial specific exams/treatment/procedures) in an investigational drug or device study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational trials. Patient is a current intravenous recreational drug user Positive serum pregnancy test in female subjects of child-bearing potential or nursing mothers or planning on becoming pregnant during the duration of the trial Patient is under guardianship Known pre-existing shunting, determined to be clinically significant by the investigator (Not applicable to Cohort B) Right ventricular dysfunction, defined by the site cardiologist as: More than mild RV dysfunction as estimated by TTE; OR TAPSE <1.4 cm; OR RV size ≥ LV size as estimated by TTE; OR Echocardiographic or clinical evidence of congestive hepatopathy Evidence of pulmonary vascular disease with PVR >3.0 Wood units Exclusion Criteria for Cohort B, Heart Failure with Pulmonary Vascular Disease only: 1. Propensity for increased Right ventricular dysfunction, defined by the site cardiologist as: More than moderate RV dysfunction as estimated by TTE; OR TAPSE <1.2 cm; OR RV size ≥ LV size as estimated by TTE; OR Mean Right Atrial Pressure (RAP) > 18 mm Hg; OR Echocardiographic or clinical evidence of congestive hepatopathy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edwards Transcatheter Atrial Shunt System<br> | Device: Transcatheter Atrial Shunt System<br>* Transcatheter treatment of symptomatic left heart failure patients<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of major adverse cardiac, cerebrovascular, or renal events (MACCRE) and re-intervention for study device related complications at 30 days. |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Success | Device is deployed as intended and the delivery system is successfully removed as intended at the time of the patient's exit from the implant procedure room. | Day 0 | 
| Procedural Success | Device success with evidence of shunt patency and hospital discharge without the need for additional surgical or percutaneous intervention related to the study device including unacceptable Qp/Qs values. | 10 days post-op | 
| Clinical Success | Procedural success without major adverse cardiac, cerebrovascular, or renal events (MACCRE) or re-intervention for study device related complications at 30 days. | 30 days | 
| Performance/Effectiveness | Comparison vs baseline of Qp/Qs value | Baseline, 3 months, 6 months | 
| Performance/Effectiveness | Improvement vs baseline of PCWP under the same test conditions (e.g. rest, legs raised, exercise) | Baseline, 3 months, 6 months | 
| Performance/Effectiveness | Change in mean, systolic & diastolic pulmonary artery pressure (PAP) and mean right atrial pressure (RAP) under the same test conditions | Baseline, 3 months, 6 months | 
| Performance/Effectiveness | Change in PVR under the same test conditions | Baseline, 3 months, 6 months | 
| Performance/Effectiveness | Change in TAPSE, TAPSE/sPAP | Baseline, 3 months, 6 months |