CoreValve® System Australia/New Zealand Clinical Study

• Freedom from Conversion to Surgery [ Time Frame: 30 Days, 6, 12, 24 months ] [ Designated as safety issue: Yes ]
• Freedom from MACCE [ Time Frame: 30 days, 6, 12, 24 months ] [ Designated as safety issue: Yes ]
• Conduction disturbances [ Time Frame: 30 days, 6, 12, 24 months ] [ Designated as safety issue: Yes ]
• Various echocardiogram measurements of replacement valve functionality [ Time Frame: 30 days, 6, 12, 24 months ] [ Designated as safety issue: No ]
• NYHA Class Improvement [ Time Frame: 30 days, 6, 12, 24 months ] [ Designated as safety issue: No ]
• All Cause Mortality [ Time Frame: In hospital, 30 days, 6, 12, 24 months ] [ Designated as safety issue: Yes ]
• Cardiac Mortality [ Time Frame: In Hospital, 30 days, 6,12, 24 months ] [ Designated as safety issue: Yes ]

To evaluate the performance, efficacy and safety of the percutaneous implantation of the CoreValve® prosthetic aortic valve in patients with severe symptomatic native aortic valve stenosis that have an elevated surgical risk

Prospective, non-randomized, single-arm multi-center trial conducted under a common protocol at 10 centers in Australia and New Zealand.

• Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Sep 23;52(13):e1-142. No abstract available.
• Varadarajan P, Kapoor N, Bansal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006 Dec;82(6):2111-5.
• Sundt TM, Bailey MS, Moon MR, Mendeloff EN, Huddleston CB, Pasque MK, Barner HB, Gay WA Jr. Quality of life after aortic valve replacement at the age of >80 years. Circulation. 2000 Nov 7;102(19 Suppl 3):III70-4.
• Kastrup J, Wennevold A, Thuesen L, Nielsen TT, Kassis E, Fritz-Hansen P, Thayssen P. Short- and long-term survival after aortic balloon valvuloplasty for calcified aortic stenosis in 137 elderly patients. Dan Med Bull. 1994 Jun;41(3):362-5.
• Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Sebagh L, Bash A, Nusimovici D, Litzler PY, Bessou JP, Leon MB. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol. 2004 Feb 18;43(4):698-703.
• Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Nercolini D, Tapiero S, Litzler PY, Bessou JP, Babaliaros V. Treatment of calcific aortic stenosis with the percutaneous heart valve: mid-term follow-up from the initial feasibility studies: the French experience. J Am Coll Cardiol. 2006 Mar 21;47(6):1214-23. Epub 2006 Feb 9.
• Grube E, Laborde JC, Gerckens U, Felderhoff T, Sauren B, Buellesfeld L, Mueller R, Menichelli M, Schmidt T, Zickmann B, Iversen S, Stone GW. Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study. Circulation. 2006 Oct 10;114(15):1616-24. Epub 2006 Oct 2.
• Grube E, Schuler G, Buellesfeld L, Gerckens U, Linke A, Wenaweser P, Sauren B, Mohr FW, Walther T, Zickmann B, Iversen S, Felderhoff T, Cartier R, Bonan R. Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome. J Am Coll Cardiol. 2007 Jul 3;50(1):69-76. Epub 2007 Jun 6.

Inclusion Criteria

1. Documented severe aortic valve stenosis
2. Access vessel diameter >6 mm as defined pre procedure via angiographic measure
3. Aortic valve annulus diameter ≥ 20 mm and < 29 mm as defined pre procedure by echocardiographic measure
4. Ascending aorta diameter ≤ 43 mm at the sino-tubular junction

5. Native aortic valve disease, defined as valve stenosis with an aortic valve area <1cm2 (<0.6cm2 /m2) as defined pre procedure by echocardiographic measure

   AND (Assessment of Surgical Risk)

   Age ≥ 80 years

   OR

   Surgical risk calculated with logistic EuroSCORE ≥ 20%,

   OR

   Age ≥ 65 years with one or two (but not more than 2) of the following criteria:

   • Cirrhosis of the liver (Child class A or B)
   • Pulmonary insufficiency : VMS < 1 liter
   • Previous cardiac surgery (CABG, valvular surgery)
   • Porcelain aorta
   • Pulmonary hypertension > 60 mmHg and high probability of cardiac surgery for other than valve replacement
   • Recurrent pulmonary embolus
   • Right ventricular insufficiency
   • Thoracic burning sequelae contraindicating open chest surgery
   • History of mediastinum radiotherapy
   • Severe connective tissue disease resulting in a contraindication to surgery
   • Cachexia (clinical impression)
6. Study subjects must be willing and able to attend all follow-up visits within specified visit windows, and agree to undergo all protocol evaluations at each visit

Exclusion Criteria:

1. Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, clopidogrel, nitinol, porcine products, or contrast media which cannot be adequately pre-medicated
2. Any sepsis, including active endocarditis.
3. Recent myocardial infarction (<30 days)
4. Any left ventricular or atrial thrombus as determined pre procedure by echocardiography
5. Uncontrolled atrial fibrillation
6. Mitral or tricuspid valvular insufficiency (> grade II)
7. Previous aortic valve replacement (mechanical valve or stented bioprosthetic valve)
8. Evolutive or recent CVA (cerebrovascular accident), (<3 months)
9. Femoral, iliac or aortic vascular condition (e.g. stenosis, tortuosity), that make impossible insertion and endovascular access to the aortic valve
10. Symptomatic carotid or vertebral arteries narrowing (> 70%) disease
11. Abdominal or thoracic aortic aneurysm
12. Bleeding diathesis or coagulopathy, or patient will refuse blood transfusion
13. Evolutive disease with life expectancy less than one year
14. Creatinine clearance < 20 ml/min
15. Active gastritis or known peptic ulcer disease
16. Pregnancy