Overview

Prospective, randomized, open-label, international, multi-center clinical study to evaluate the safety and efficacy of the AccuCinch Ventricular Restoration System in patients with heart failure and reduced ejection fraction (HFrEF).

Eligibility

Inclusion Criteria:

1. Age 18-years or older
2. Ejection Fraction: ≥20% and ≤40% measured by transthoracic echocardiography (TTE) and assessed by an echocardiography (echo) core lab
3. LV end-diastolic diameter ≥55 mm measured by TTE and assessed by an echo core lab
4. Symptom Status:
   1. NYHA III,
   2. NYHA ambulatory IV, or
   3. NYHA II with a heart failure hospitalization within the prior 12 months (of signing the consent)
5. Able to complete six-minute walk test with distance between 100 m and 450 m.
6. Diagnosis and treatment for heart failure should be established at least 90 days before the date of consent. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current guidelines as standard-of-care for Heart Failure therapy, with any intolerance documented.
   1. "Stable" is defined as no more than a 100% increase or a 50% decrease of total daily doses. Medication changes within this range do not require any additional waiting before the screening assessments
   2. When a total daily dose increase or decrease exceeds that which is considered stable, the screening TTE and CT will be postponed 30 days after the medication change
   3. When additional titration is required to optimize a subject's medication that exceeds what is considered stable, the screening TTE and CT will be postponed at least 30 days after achieving the optimal dose (provided the optimal dose remains outside of the stable parameters)
   4. When a dose-for-dose equivalent change in the class of medication change is made, no additional waiting is required before the screening assessments
   5. When a change in class medication change exceeds what is considered stable, OR a new class of medication is added, the screening TTE and CT will be postponed 30 days after the medication change
   6. If an SGLT2 inhibitor is added to a subject's medications, the screening TTE and CT will be postponed at least 30 days after the addition
   7. If an SGLT2 inhibitor dose changes per the stable definition above, no additional waiting is required before the screening assessments
   8. If an SGLT2 inhibitor dose change exceeds what is considered stable, the screening TTE and CT will be postponed at least 30 days after achieving the optimal dose (provided the dose remains outside of the stable parameters)
   9. When applicable, for guideline-directed device-based therapies: a CRT device must be placed > 90 days before the screening TTE and CT, and an ICD must be placed > 30 days before the screening TTE and CT
7. Able and willing to complete all qualifying diagnostic and functional tests, willing

   to accept blood product transfusion if required and agrees to comply with study follow-up schedule

Exclusion Criteria:

Cardiovascular

1. Myocardial infarction or any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 90 days prior to consent
2. Untreated clinically significant coronary artery disease (CAD) requiring revascularization
3. Fluoroscopic or echocardiographic evidence of severe aortic arch calcification, mobile aortic atheroma, intracardiac mass, thrombus or vegetation
4. Suboptimal ventricular anatomy or wall thickness as determined from screening echocardiography and/or CT scan
5. Heart failure on the basis other than ischemic or non-ischemic dilated cardiomyopathy (e.g., hypertrophic cardiomyopathy, amyloid cardiomyopathy, restrictive cardiomyopathy, uncorrected congenital heart disease, constrictive pericarditis)
6. Hemodynamic instability within 30 days prior to the implant defined as subject requiring inotropic support or mechanical hemodynamic support
7. Any planned cardiac surgery or interventions within the next 180 days post-randomization (including therapeutic right heart procedures)
8. Active bacterial endocarditis
9. Severe RV dysfunction assessed by right heart catheterization (RHC) and/or TTE
10. Fixed pulmonary hypertension with PA systolic pressure >70 mmHg not responsive to vasodilator therapy
11. History of any stroke within the prior 90 days of consent or documented Modified Rankin Scale ≥ 2 disability from any prior stroke

    Valvular

12. Mitral regurgitation grade 3+ (moderate-severe) or 4+ (severe)
13. Untreated degenerative (primary) mitral valve disease (mild prolapse with no need for intervention is allowable)
14. Prior mitral or aortic valve replacement
15. Tricuspid regurgitation grade 4+ (severe)
16. Moderate or severe aortic valve stenosis (AVA less than 1.5 cm2 or peak velocity AV Vmax >300 cm/sec)
17. Aortic regurgitation grade 2+ (moderate), 3+ (moderate-severe), or 4+ (severe)

    Procedural

18. Anatomical pathology or constraints preventing appropriate access/implant of the AccuCinch Ventricular Restoration System (e.g., femoral arteries will not support a 20F Introducer sheath)
19. Renal insufficiency (i.e., eGFR of <25 ml/min/1.73 m2)
20. Subjects in whom anticoagulation during the procedure is contraindicated
21. Subjects in whom 90 days of antiplatelet therapy is contraindicated
22. Known allergy to nitinol, polyester, or polyethylene
23. Any prior true anaphylactic reaction to contrast agents; defined as known anaphylactoid or other non-anaphylactic allergic reactions to contrast agents that cannot be adequately pre-medicated prior to the index procedure

    General

24. Life expectancy <1 year due to non-cardiac conditions
25. Currently participating in another interventional investigational study
26. Subjects on high dose steroids or immunosuppressant therapy
27. Female subjects who are pregnant, of child-bearing potential without a documented birth control method, or who are lactating