Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure

Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure

The purpose of this study is to evaluate the safety and effectiveness of the HeartWare® LVAD System in patients listed for cardiac transplantation with refractory, advanced heart failure at risk of death. The primary endpoint is survival at 180 days which is defined as alive on the originally implanted HeartWare® LVAD or transplanted or explanted for recovery. Patient must survive 60 days post-explant for recovery to be considered successful. Secondary endpoints include:

• Overall survival
• Incidence of all serious adverse events, neurocognitive status and unanticipated adverse device effects.
• Incidence of all device failures and device malfunctions
• Quality of Life improvement, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQoL EQ-5D
• Functional status improvement, as measured by the New York Heart Association (NYHA) and 6-minute walk

The HeartWare® LVAD System was approved by the US FDA on November 20, 2012 as a bridge to cardiac transplantation (reference PMA P100047). Patients enrolled into this study will be followed to an outcome at six months, and then patients will receive continued follow-up in a separate study.

Inclusion Criteria:

1. Must be at least 18 years of age at enrollment.
2. Body Surface Area (BSA) greater than or equal to 1.2 m2.
3. Patient is NYHA Class IV
4. Patient listed for cardiac transplantation
5. Patient meets United Network for Organ Sharing (UNOS) Status 1A or 1B listing criteria.
6. HeartWare® LVAD implant is planned as a bridge to transplant
7. The patient or legally authorized representative has signed the informed consent form

Exclusion Criteria:

1. Existence of any ongoing mechanical circulatory support (MCS) other than an intra-aortic balloon pump (IABP)

2. Prior cardiac transplant.

3. History of confirmed, untreated abdominal or thoracic aortic aneurysm > 5 cm.

4. Cardiothoracic surgery within 30 days of enrollment.

5. Acute myocardial infarction within 14 days of implant as diagnosed by ST or T wave changes on the ECG, diagnostic biomarkers, ongoing pain and hemodynamic abnormalities as described (Figure 2) in the guidelines published in ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction; A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JACC Vol. 50, No.7, 2007.

6. On ventilator support for > 72 hours within the fours days immediately prior to enrollment.

7. Pulmonary embolus within three weeks of enrollment as documented by computed tomography (CT) scan or nuclear scan.

8. Symptomatic cerebrovascular disease or a > 80% carotid stenosis.

9. Patients have moderate to severe aortic insufficiency without plans for correction during pump implantation surgery.

10. Patients with mechanical, animal or human tissue heart valves are excluded.

11. Severe right ventricular failure as defined by the anticipated need for right ventricular assist device (RVAD) support or extracorporeal membrane oxygenation (ECMO)at the time of HeartWare® LVAD screening/enrollment or right atrial pressure > 20 mmHg on multiple inotropes, right ventricular ejection fraction (RVEF) <15% or clinical signs including lower extremity edema, ascites or pleural effusions refractory to treatment with diuretics and two inotropic drugs.

12. Active, uncontrolled infection diagnosed by a combination of clinical symptoms and laboratory testing, including but not limited to, continued positive cultures, elevated temperature and white blood cell (WBC) count, hypotension, tachycardia, generalized malaise despite appropriate antibiotic, antiviral or antifungal treatment.

13. Uncorrected thrombocytopenia or generalized coagulopathy (e.g., platelet count < 100,000, INR > 1.6 or PTT > 2.5 times control in the absence of anticoagulation therapy).

14. 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.

15. Serum creatinine greater than 3.0 times the upper limit of normal within 48 hours of study enrollment or requiring dialysis (does not include use of ultra-filtration for fluid removal).

16. All three listed liver enzymes [AST (SGOT), ALT (SGPT), or LDH] > 3 times upper limit of normal or a total bilirubin > 3 mg/dl within 24 hours of study enrollment, or biopsy proven liver cirrhosis or portal hypertension.

17. 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 three following variables:

    • Pulmonary vascular resistance is greater than 5 Woods Units or
    • Pulmonary vascular resistance index is greater than 6 Woods Units or
    • Transpulmonary gradient exceeds 16 to 20 mmHg

18. Patients requiring aortic, mitral, tricuspid or pulmonary valve replacements (including bioprosthetic valves) or left ventricular (LV) aneurysm resections.

19. Participation in any other study involving investigational drugs or devices.

20. Severe illness, other than heart disease, which would exclude cardiac transplantation.

21. Pregnancy.

22. Patient unwilling or unable to comply with study requirements.