Clinical Evaluation of HW005 Ventricular Assist System for the Treatment of Advanced Heart Failure in Japan

The primary endpoint is success at 180 days which is expressed as a simple proportion and defined as alive on the originally implanted HW005 or transplanted or explanted for recovery. Patients must survive 60 days post-explant for recovery to be considered successful. The primary endpoint is not statistically powered. The six eligible implanted cases will be evaluated as a proportion of success accompanied by a 95% exact confidence interval and presented alongside the ADVANCE results for visual comparison.

Inclusion criteria

• Patients with irreversible end-stage heart failure of New York Heart Association (NYHA) class III or IV and a history of class IV who are eligible for heart transplantation.
• Patients who are dependent on medication of inotropes or intra-aortic balloon pump (IABP).
• Body Surface Area (BSA) ≥1.2 m2. In addition other factors may be taken into consideration, including chest size, abdominal fat (lack of abdominal fat may preclude a pump pocket) and any other physical characteristics that might be benefited by an intra-pericardial pump in a small person.
• Patients who are aged less than 65 years of age.
• Patients must be able to understand the limits and complications associated with the HW005 Ventricular Assist System.
• Female patients of childbearing potential must agree on contraception for the duration of the study.
• The patient or the legal representative has signed the informed consent form.

Exclusion criteria

• Severe illness other than heart disease which would exclude cardiac transplantation.
• Inadequate family/social support.
• Active, uncontrolled infection despite appropriate antibiotic, antiviral or antifungal treatment.
• Existence of any ongoing mechanical circulatory support (MCS) other than an IABP.
• Prior cardiac transplant or cardiomyoplasty.
• Acute myocardial infarction within 14 days of implant.
• Uncorrected thrombocytopenia or generalized coagulopathy.
• Intolerance to anticoagulant or antiplatelet therapies or any other peri- or postoperative therapy that the investigator may administer based upon the patient's health status.
• Patients for whom the use of a left ventricular assist device (LVAD) is contraindicated due to an ongoing aortic/cardiac aneurysm, intraventricular septum rupture and/or use of a mechanical heart valve.
• Etiology of heart failure is due to, or associated with, uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis, active myocarditis or restrictive cardiomyopathy.
• Patients with irreversible hepatic dysfunction.
• Patients with irreversible renal dysfunction.
• Pregnancy.
• Patients with serious chronic obstructive pulmonary disease (COPD) (Forced Expiratory Volume in the first second (FEV1) < 50%).
• Pulmonary vascular resistance is unresponsive (fixed) to pharmacologic manipulation as demonstrated by a pulmonary artery systolic pressure exceeding 60mmHg in conjunction with any one of the two following variables:

• Pulmonary vascular resistance is greater than 6 Woods Units or
• Transpulmonary gradient exceeds 15 mmHg
• Cardiothoracic surgery within 14 days of implantation.
• Peripheral vascular disease with rest pain or ischemic ulcers of the extremities.
• Pulmonary embolus within three weeks of enrollment as documented by computed tomography (CT) scan or nuclear scan.
• Patients have moderate to severe aortic insufficiency without plans for correction during pump implantation surgery. Correction may include aortic valve repair at the time of implant.
• The patient who has advanced calcification in the ascending aorta and/or the descending aorta.
• Serious right heart failure as defined by the anticipated need for right ventricular assist device (RVAD) support or extracorporeal membrane oxygenation (ECMO) at the time of screening.
• Patients with severe central nervous system disorder or severe cerebral vascular disorder.
• Patients with a history of drug intoxication, alcohol dependence.
• Patients unwilling or unable to comply with study requirements.
• Patients who refuse transfusion.
• Patients who in the investigator judgement are deemed to be unsuitable as a subject.
• Patients who are participating in another clinical trial involving investigational drugs or devices.