Aortic Stenosis Facts

The population at risk for aortic stenosis is growing. It is estimated that 2.5 million people in the US over the age of 75 suffer from this disease,1 which is about 12.4% of that population.2 The elderly population will more than double between now and the year 2050, to 80 million.3

Aortic stenosis is also more likely to affect men than women. 80% of adults with symptomatic aortic stenosis are male.5

Severe Aortic Stenosis is Life Threatening and Treatment is Critical6

Patients may live with aortic stenosis for many years during a latent, asymptomatic period, even before symptoms of the disease develop and present. However, after patients begin experiencing symptoms, it is urgent they receive treatment.

After the onset of symptoms, patients with severe aortic stenosis have a survival rate as low as 50% at 2 years and 20% at 5 years without aortic valve replacement.5

Approximately 12.4% of the population over the age of 75 have aortic stenosis. 1,2

Impact of Untreated, Symptomatic Aortic Stenosis on Patients

Quality of Life is Significantly Impacted

Patients with severe aortic stenosis often develop symptoms that can restrict normal day-to-day activities, such as walking short distances or climbing stairs. These patients can often benefit from replacing their ailing valve, but only approximately two-thirds of them undergo the procedure each year.7

Timely Intervention is Critical for Patients with Symptoms8

Once symptoms appear, untreated patients have a poor prognosis.8 Without treatment, symptomatic aortic stenosis will eventually lead to death.

Average Course for Adults With Valvular Aortic Stenosis6

Severe Aortic Stenosis Has a Worse Prognosis Than Many Metastatic Cancers*,9

5-year survival rate (distant metastatis) of lung cancer, colorectal cancer, breast cancer, ovarian cancer and prostate cancer compared to severe inoperable aortic stenosis.

0
0
0
0
0
0
Severe Inoperable
Aortic Stenosis*
Lung
Cancer
Colorectal
Cancer
Breast
Cancer
Ovarian
Cancer
Prostate
Cancer
*Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic

50

After the onset of symptoms, patients with severe aortic stenosis have a survival rate as low as 50% at 2 years and 20% at 5 years without aortic valve replacement4

While Treatment Can Improve Survival, Most Patients Go Untreated

Aortic valve replacement is the only effective treatment considered a Class I recommendation by the American College of Cardiology and the American Heart Association.10 However, multiple studies confirm that, more often than not, patients are not receiving aortic valve replacement.7,11-16

At least 40% (and perhaps up to 60%) of patients with severe aortic stenosis do not receive valve replacement. 7,11-16

References:
1. U.S. Census Bureau, Population Division. June 2015.
2. Osnabrugge, Ruben L.J., et al. Aortic Stenosis in the Elderly. Disease Prevalence and Number Candidates for Transcatheter Aortic Valve Replacement: A Meta-Analysis and Modeling Study. J Am Coll Cardiol. 2013;62:1002-1012.
3. U.S. Census Bureau Statistical Brief. May 1995.
4. Ramaraj R, Sorrell V. Degenerative aortic stenosis. BMJ 2008;336:550-5.
5. Otto C. VALVE DISEASE: Timing of aortic valve surgery. Heart. 2000;84(2):211-218.
6. Lester S, Heilbron B, Dodek A, Gin K, Jue J. The Natural History and Rate of Progression of Aortic Stenosis. Chest. 1998;113(4):1109.
7. Bach D, Siao D, Girard S, Duvernoy C, McCallister B, Gualano S. Evaluation of Patients With Severe Symptomatic Aortic Stenosis Who Do Not Undergo Aortic Valve Replacement: The Potential Role of Subjectively Overestimated Operative Risk. Circ Cardiovasc Qual Outcomes. 2009;2(6):533-539.
8. Nishimura R, Otto C, Bonow R, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary. J Am Coll Cardiol. 2014;63(22):2438-2488.
9. National Cancer Institute. SEER Cancer Stat Fact Sheets. Seercancergov. Available at: http://seer.cancer.gov/statfacts/. Accessed November 16, 2010.
10. Stewart B, Siscovick D, Lind B, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol. 1997;29(3):630-634.
11. Freed B, Sugeng L, Furlong K et al. Reasons for Nonadherence to Guidelines for Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Potential Solutions. Am J Cardiol. 2010;105(9):1339-1342.
12. Bouma B, van den Brink R, van der Meulen J, et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart. 1999;82(2):143-148.
13. Pellikka P, Sarano M, Nishimura R, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation. 2005;111(24):3290-3295.
14. Charlson E, Legedza A, Hamel M. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis. 2006;15(3):312-321.
15. Varadarajan P, Kapoor N, Banscal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006;82(6):2111-2115.
16. Jan F, Andreev M, Mori N, Janosik B, Sagar K. Unoperated patients with severe symptomatic aortic stenosis. Circulation. 2009;120;S753.

Important Safety Information

Indications: The Edwards SAPIEN 3 transcatheter heart valve, model 9600TFX, and accessories are indicated for relief of aortic stenosis in patients with symptomatic heart disease...

Important Safety Information

Open

EDWARDS SAPIEN 3 TRANSCATHETER HEART VALVE WITH THE EDWARDS COMMANDER DELIVERY SYSTEM

Indications: The Edwards SAPIEN 3 transcatheter heart valve, model 9600TFX, and accessories are indicated for relief of aortic stenosis in patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a Heart Team, including a cardiac surgeon, to be at intermediate or greater risk for open surgical therapy (i.e., predicted risk of surgical mortality ≥ 3% at 30 days, based on the Society of Thoracic Surgeons (STS) risk score and other clinical co-morbidities unmeasured by the STS risk calculator).

Contraindications: The valve and delivery systems are contraindicated in patients who cannot tolerate an anticoagulation/antiplatelet regimen or who have active bacterial endocarditis or other active infections.

Warnings: Observation of the pacing lead throughout the procedure is essential to avoid the potential risk of pacing lead perforation. There may be an increased risk of stroke in transcatheter aortic valve replacement procedures, as compared to balloon aortic valvuloplasty or other standard treatments in high or greater risk patients. The devices are designed, intended, and distributed for single use only. Do not resterilize or reuse the devices. There are no data to support the sterility, nonpyrogenicity, and functionality of the devices after reprocessing. Incorrect sizing of the valve may lead to paravalvular leak, migration, embolization, and/or annular rupture. Accelerated deterioration of the valve may occur in patients with an altered calcium metabolism. Prior to delivery, the valve must remain hydrated at all times and cannot be exposed to solutions other than its shipping storage solution and sterile physiologic rinsing solution. Valve leaflets mishandled or damaged during any part of the procedure will require replacement of the valve. Caution should be exercised in implanting a valve in patients with clinically significant coronary artery disease. Patients with pre-existing mitral valve devices should be carefully assessed prior to implantation of the valve to ensure proper valve positioning and deployment. Do not mishandle the delivery system or use it if the packaging or any components are not sterile, have been opened or are damaged (e.g., kinked or stretched), or if the expiration date has elapsed. Use of excessive contrast media may lead to renal failure. Measure the patient’s creatinine level prior to the procedure. Contrast media usage should be monitored. Patient injury could occur if the delivery system is not un-flexed prior to removal. Care should be exercised in patients with hypersensitivities to cobalt, nickel, chromium, molybdenum, titanium, manganese, silicon, and/or polymeric materials. The procedure should be conducted under fluoroscopic guidance. Some fluoroscopically guided procedures are associated with a risk of radiation injury to the skin. These injuries may be painful, disfiguring, and long-lasting. Valve recipients should be maintained on anticoagulant/antiplatelet therapy, except when contraindicated, as determined by their physician. This device has not been tested for use without anticoagulation.

Precautions: Long-term durability has not been established for the valve. Regular medical follow-up is advised to evaluate valve performance. Glutaraldehyde may cause irritation of the skin, eyes, nose, and throat. Avoid prolonged or repeated exposure to, or breathing of, the solution. To maintain proper valve leaflet coaptation, do not overinflate the deployment balloon. Appropriate antibiotic prophylaxis is recommended post-procedure in patients at risk for prosthetic valve infection and endocarditis. Safety, effectiveness, and durability have not been established for valve-in-valve procedures. Safety and effectiveness have not been established for patients with the following characteristics/comorbidities: non-calcified aortic annulus; severe ventricular dysfunction with ejection fraction < 20%; congenital unicuspid or congenital bicuspid aortic valve; mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation > 3+); pre-existing prosthetic heart valve or prosthetic ring in any position; severe mitral annular calcification (MAC), severe (> 3+) mitral insufficiency, or Gorlin syndrome; blood dyscrasias defined as leukopenia (WBC < 3000 cells/mL), acute anemia (Hb < 9 g/dL), thrombocytopenia (platelet count < 50,000 cells/mL), or history of bleeding diathesis or coagulopathy; hypertrophic cardiomyopathy with or without obstruction (HOCM); echocardiographic evidence of intracardiac mass, thrombus, or vegetation; a known hypersensitivity or contraindication to aspirin, heparin, ticlopidine (Ticlid), or clopidogrel (Plavix), or sensitivity to contrast media, which cannot be adequately premedicated; significant aortic disease, including abdominal aortic or thoracic aneurysm defined as maximal luminal diameter 5 cm or greater, marked tortuosity (hyperacute bend), aortic arch atheroma (especially if thick [> 5 mm], protruding, or ulcerated) or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe “unfolding” and tortuosity of the thoracic aorta; access characteristics that would preclude safe placement of 14F or 16F Edwards eSheath introducer set, such as severe obstructive calcification, severe tortuosity, or diameter less than 5.5 mm or 6 mm, respectively; or bulky calcified aortic valve leaflets in close proximity to coronary ostia.

Potential Adverse Events: Potential risks associated with the overall procedure including potential access complications associated with standard cardiac catheterization, balloon valvuloplasty, the potential risks of conscious sedation and/or general anesthesia, and the use of angiography: death; stroke/transient ischemic attack, clusters, or neurological deficit; paralysis; permanent disability; respiratory insufficiency or respiratory failure; hemorrhage requiring transfusion or intervention; cardiovascular injury including perforation or dissection of vessels, ventricle, myocardium, or valvular structures that may require intervention; pericardial effusion or cardiac tamponade; embolization including air, calcific valve material, or thrombus; infection including septicemia and endocarditis; heart failure; myocardial infarction; renal insufficiency or renal failure; conduction system defect which may require a permanent pacemaker; arrhythmia; retroperitoneal bleed; arteriovenous (AV) fistula or pseudoaneurysm; reoperation; ischemia or nerve injury; restenosis; pulmonary edema; pleural effusion; bleeding; anemia; abnormal lab values (including electrolyte imbalance); hypertension or hypotension; allergic reaction to anesthesia, contrast media, or device materials; hematoma; syncope; pain or changes at the access site; exercise intolerance or weakness; inflammation; angina; heart murmur; and fever. Additional potential risks associated with the use of the valve, delivery system, and/or accessories include: cardiac arrest; cardiogenic shock; emergency cardiac surgery; cardiac failure or low cardiac output; coronary flow obstruction/ transvalvular flow disturbance; device thrombosis requiring intervention; valve thrombosis; device embolization; device migration or malposition requiring intervention; valve deployment in unintended location; valve stenosis; structural valve deterioration (wear, fracture, calcification, leaflet tear/tearing from the stent posts, leaflet retraction, suture line disruption of components of a prosthetic valve, thickening, stenosis); device degeneration; paravalvular or transvalvular leak; valve regurgitation; hemolysis; device explants; nonstructural dysfunction; mechanical failure of delivery system and/or accessories; and non-emergent reoperation.

EDWARDS CRIMPER

Indications: The Edwards Crimper is indicated for use in preparing the Edwards SAPIEN 3 transcatheter heart valve for implantation.

Contraindications: There are no known contraindications.

Warnings: The devices are designed, intended, and distributed for single use only. Do not resterilize or reuse the devices. There is no data to support the sterility, nonpyrogenicity, and functionality of the devices after reprocessing.

Precautions: For special considerations associated with the use of the Edwards Crimper prior to valve implantation, refer to the Edwards SAPIEN 3 transcatheter heart valve Instructions for Use.

Potential Adverse Events: There are no known potential adverse events associated with the Edwards Crimper.

EDWARDS SAPIEN XT TRANSCATHETER HEART VALVE WITH THE NOVAFLEX+ DELIVERY SYSTEM

Indications: The Edwards SAPIEN XT transcatheter heart valve, model 9300TFX, and accessories are indicated for relief of aortic stenosis in patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a Heart Team, including a cardiac surgeon, to be at intermediate or greater risk for open surgical therapy (i.e., predicted risk of surgical mortality ≥ 3% at 30 days, based on the Society of Thoracic Surgeons (STS) risk score and other clinical co-morbidities unmeasured by the STS risk calculator). The Edwards SAPIEN XT transcatheter heart valve and accessories are also indicated for patients with symptomatic heart disease due to failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., STS operative risk score ≥8% or at a ≥15% risk of mortality at 30 days).

Contraindications: The valve and delivery systems are contraindicated in patients who cannot tolerate an anticoagulation/antiplatelet regimen or who have active bacterial endocarditis or other active infections.

Warnings: Observation of the pacing lead throughout the procedure is essential to avoid the potential risk of pacing lead perforation. There may be an increased risk of stroke in transcatheter aortic valve replacement procedures, as compared to balloon aortic valvuloplasty or other standard treatments in high or greater risk patients. The devices are designed, intended, and distributed for single use only. Do not resterilize or reuse the devices. There are no data to support the sterility, nonpyrogenicity, and functionality of the devices after reprocessing. Care should be exercised when sizing the native annulus or surgical valve; implanting a valve that is too small may lead to paravalvular leak, migration or embolization, whereas implanting a valve that is too large may lead to residual gradient (patient-prosthesis mismatch) or annular rupture. Accelerated deterioration of the valve may occur in patients with an altered calcium metabolism. Prior to delivery, the valve must remain hydrated at all times and cannot be exposed to solutions other than its shipping storage solution and sterile physiologic rinsing solution. Valve leaflets mishandled or damaged during any part of the procedure will require replacement of the valve. Caution should be exercised in implanting a valve in patients with clinically significant coronary artery disease. Patients with pre-existing mitral valve devices should be carefully assessed prior to implantation of the valve to ensure proper valve positioning and deployment. Do not use the valve if the tamper evident seal is broken, the storage solution does not completely cover the valve, the temperature indicator has been activated, the valve is damaged, or the expiration date has elapsed. Do not mishandle the NovaFlex+ delivery system or use it if the packaging or any components are not sterile, have been opened or are damaged (e.g. kinked or stretched), or the expiration date has elapsed. Use of excessive contrast media may lead to renal failure. Measure the patient’s creatinine level prior to the procedure. Contrast media usage should be monitored. Patient injury could occur if the delivery system is not un-flexed prior to removal. Care should be exercised in patients with hypersensitivities to cobalt, nickel, chromium, molybdenum, titanium, manganese, silicon, and/or polymeric materials. The procedure should be conducted under fluoroscopic guidance. Some fluoroscopically guided procedures are associated with a risk of radiation injury to the skin. These injuries may be painful, disfiguring, and long-lasting. Valve recipients should be maintained on anticoagulant/antiplatelet therapy, except when contraindicated, as determined by their physician. This device has not been tested for use without anticoagulation. Do not add or apply antibiotics to the storage solution, rinse solutions, or to the valve.

Precautions: Long-term durability has not been established for the valve. Regular medical follow-up is advised to evaluate valve performance. Glutaraldehyde may cause irritation of the skin, eyes, nose and throat. Avoid prolonged or repeated exposure to, or breathing of, the solution. Use only with adequate ventilation. If skin contact occurs, immediately flush the affected area with water; in the event of contact with eyes, seek immediate medical attention. For more information about glutaraldehyde exposure, refer to the Material Safety Data Sheet available from Edwards Lifesciences. To maintain proper valve leaflet coaptation, do not overinflate the deployment balloon. Appropriate antibiotic prophylaxis is recommended post-procedure in patients at risk for prosthetic valve infection and endocarditis. Safety, effectiveness, and durability have not been established for transcatheter valve in transcatheter valve procedures. Safety and effectiveness have not been established for patients with the following characteristics/comorbidities: non-calcified aortic annulus, severe ventricular dysfunction with ejection fraction < 20%, congenital unicuspid or congenital bicuspid aortic valve, mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation > 3+), pre-existing prosthetic ring in any position, severe mitral annular calcification (MAC), severe (> 3+) mitral insufficiency, or Gorlin syndrome, blood dyscrasias defined as: leukopenia (WBC < 3000 cells/mL), acute anemia (Hb < 9 g/dL), thrombocytopenia (platelet count <50,000 cells/mL), or history of bleeding diathesis or coagulopathy, hypertrophic cardiomyopathy with or without obstruction (HOCM), echocardiographic evidence of intracardiac mass, thrombus, or vegetation, a known hypersensitivity or contraindication to aspirin, heparin, ticlopidine (Ticlid), or clopidogrel (Plavix), or sensitivity to contrast media, which cannot be adequately premedicated, significant aortic disease, including abdominal aortic or thoracic aneurysm defined as maximal luminal diameter 5 cm or greater; marked tortuosity (hyperacute bend), aortic arch atheroma (especially if thick [> 5 mm], protruding, or ulcerated) or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe “unfolding” and tortuosity of the thoracic aorta, access characteristics that would preclude safe placement of 16F, 18F, or 20F Edwards expandable introducer sheath set, such as severe obstructive calcification, severe tortuosity or diameter less than 6 mm, 6.5 mm, or 7 mm, respectively, bulky calcified aortic valve leaflets in close proximity to coronary ostia, a concomitant paravalvular leak where the surgical bioprosthesis is not securely fixed in the native annulus or is not structurally intact (e.g. wireform frame fracture), and a partially detached leaflet of the surgical bioprosthesis that in the aortic position may obstruct a coronary ostium. The safety and effectiveness have not been established for implanting the transcatheter valve inside a stented bioprosthetic valve < 21 mm (labeled size) or an unstented bioprosthetic aortic valve. Residual mean gradient may be higher in a “TAV-in-SAV” configuration than that observed following implantation of the valve inside a native aortic annulus using the same size device. Patients with elevated mean gradient post procedure should be carefully followed. It is important that the manufacturer, model and size of the preexisting surgical bioprosthetic aortic valve be determined, so that the appropriate valve can be implanted and a prosthesis-patient mismatch be avoided. Additionally, pre-procedure imaging modalities must be employed to make as accurate a determination of the internal orifice as possible.

Potential Adverse Events: Potential risks associated with the overall procedure including potential access complications associated with standard cardiac catheterization, balloon valvuloplasty, the potential risks of conscious sedation and/or general anesthesia, and the use of angiography: death; stroke/transient ischemic attack, clusters or neurological deficit; paralysis; permanent disability; respiratory insufficiency or respiratory failure; hemorrhage requiring transfusion or intervention; cardiovascular injury including perforation or dissection of vessels, ventricle, myocardium or valvular structures that may require intervention; pericardial effusion or cardiac tamponade; embolization including air, calcific valve material or thrombus; infection including septicemia and endocarditis; heart failure; myocardial infarction; renal insufficiency or renal failure; conduction system defect which may require a permanent pacemaker; arrhythmia; retroperitoneal bleed; Arteriovenous (AV) fistula or pseudoaneurysm; reoperation; ischemia or nerve injury; restenosis; pulmonary edema; pleural effusion; bleeding; anemia; abnormal lab values (including electrolyte imbalance); hypertension or hypotension; allergic reaction to anesthesia, contrast media, or device materials; hematoma; syncope; pain or changes at the access site; exercise intolerance or weakness; inflammation; angina; heart murmur; fever. Additional potential risks associated with the use of the valve, delivery system, and/or accessories include: cardiac arrest; cardiogenic shock; emergency cardiac surgery; cardiac failure or low cardiac output; coronary flow obstruction/transvalvular flow disturbance; device thrombosis requiring intervention; valve thrombosis; device embolization; device migration or malposition requiring intervention; valve deployment in unintended location; valve stenosis; structural valve deterioration (wear, fracture, calcification, leaflet tear/tearing from the stent posts, leaflet retraction, suture line disruption of components of a prosthetic valve, thickening, stenosis); device degeneration; paravalvular or transvalvular leak; valve regurgitation; hemolysis; device explants; nonstructural dysfunction; mechanical failure of delivery system, and/or accessories, non-emergent reoperation.

EDWARDS EXPANDABLE INTRODUCER SHEATH SET

Indications: The Edwards expandable introducer sheath is indicated for the introduction and removal of devices used with the Edwards SAPIEN XT transcatheter heart valve.

Contraindications: This product is contraindicated for tortuous or calcified vessels that would prevent safe entry of the introducer and sheath.

Warnings: The devices are designed, intended, and distributed for single use only. Do not resterilize or reuse the devices. There is no data to support the sterility, nonpyrogenicity, and functionality of the devices after reprocessing. The Edwards expandable introducer sheath set must be used with a compatible 0.035” guidewire.

Precautions: Do not use the introducer sheath set if the packaging sterile barriers and any components have been opened or damaged. The Edwards Expandable Sheath temporarily enlarges to allow the passage of devices; ensure that the vasculature can accommodate the maximum diameter of the expanded sheath. When inserting, manipulating or withdrawing a device through the expandable sheath, always maintain sheath position. When puncturing, suturing or incising the tissue near the sheath, use caution to avoid damage to the sheath.

Potential Adverse Events: Complications associated with standard catheterization and use of angiography include, but are not limited to, injury including perforation or dissection of vessels, thrombosis, and/or plaque dislodgement which may result in emboli formation, distal vessel obstruction, stroke, infection, and/or death.

EDWARDS SAPIEN XT TRANSCATHETER HEART VALVE WITH THE Ascendra+ DELIVERY SYSTEM

Indications: The Edwards SAPIEN XT transcatheter heart valve, model 9300TFX, and accessories are indicated for relief of aortic stenosis in patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a Heart Team, including a cardiac surgeon, to be at intermediate or greater risk for open surgical therapy (i.e., predicted risk of surgical mortality ≥ 3% at 30 days, based on the Society of Thoracic Surgeons (STS) risk score and other clinical co-morbidities unmeasured by the STS risk calculator). The Edwards SAPIEN XT transcatheter heart valve and accessories are also indicated for patients with symptomatic heart disease due to failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., STS operative risk score ≥8% or at a ≥15% risk of mortality at 30 days).

Contraindications: The valve and delivery systems are contraindicated in patients who cannot tolerate an anticoagulation/antiplatelet regimen or who have active bacterial endocarditis or other active infections.

Warnings: Observation of the pacing lead throughout the procedure is essential to avoid the potential risk of pacing lead perforation. There may be an increased risk of stroke in transcatheter aortic valve replacement procedures, as compared to balloon aortic valvuloplasty or other standard treatments in high or greater risk patients. The devices are designed, intended, and distributed for single use only. Do not resterilize or reuse the devices. There are no data to support the sterility, nonpyrogenicity, and functionality of the devices after reprocessing. Care should be exercised when sizing the native annulus or surgical valve; implanting a valve that is too small may lead to paravalvular leak, migration or embolization, whereas implanting a valve that is too large may lead to residual gradient (patient-prosthesis mismatch) or annular rupture. Accelerated deterioration of the valve may occur in patients with an altered calcium metabolism. Prior to delivery, the valve must remain hydrated at all times and cannot be exposed to solutions other than its shipping storage solution and sterile physiologic rinsing solution. Valve leaflets mishandled or damaged during any part of the procedure will require replacement of the valve. Caution should be exercised in implanting a valve in patients with clinically significant coronary artery disease. Patients with pre-existing mitral valve devices should be carefully assessed prior to implantation of the valve to ensure proper valve positioning and deployment. Patients presenting with combination AV low flow, low gradient should undergo additional evaluation to establish the degree of aortic stenosis. Do not use the valve if the tamper evident seal is broken, the storage solution does not completely cover the valve, the temperature indicator has been activated, the valve is damaged, or the expiration date has elapsed. Do not mishandle the Ascendra+ delivery system or use it if the packaging or any components are not sterile, have been opened or are damaged (e.g. kinked or stretched), or the expiration date has elapsed. Care should be exercised in patients with hypersensitivities to cobalt, nickel, chromium, molybdenum, titanium, manganese, silicon, and/or polymeric materials. The procedure should be conducted under fluoroscopic guidance. Some fluoroscopically guided procedures are associated with a risk of radiation injury to the skin. These injuries may be painful, disfiguring, and long-lasting. Valve recipients should be maintained on anticoagulant/antiplatelet therapy, except when contraindicated, as determined by their physician. This device has not been tested for use without anticoagulation. Do not add or apply antibiotics to the storage solution, rinse solutions, or to the valve.

Precautions: Long-term durability has not been established for the valve. Regular medical follow-up is advised to evaluate valve performance. Glutaraldehyde may cause irritation of the skin, eyes, nose and throat. Avoid prolonged or repeated exposure to, or breathing of, the solution. Use only with adequate ventilation. If skin contact occurs, immediately flush the affected area with water; in the event of contact with eyes, seek immediate medical attention. For more information about glutaraldehyde exposure, refer to the Material Safety Data Sheet available from Edwards Lifesciences. To maintain proper valve leaflet coaptation, do not overinflate the deployment balloon. Appropriate antibiotic prophylaxis is recommended post-procedure in patients at risk for prosthetic valve infection and endocarditis. Safety, effectiveness, and durability have not been established for transcatheter valve in transcatheter valve procedures. Safety and effectiveness have not been established for patients with the following characteristics/comorbidities: Non-calcified aortic annulus, severe ventricular dysfunction with ejection fraction < 20%, congenital unicuspid or congenital bicuspid aortic valve, mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation > 3+), pre-existing prosthetic ring in any position, severe mitral annular calcification (MAC), severe (> 3+) mitral insufficiency, or Gorlin syndrome, blood dyscrasias defined as: leukopenia (WBC < 3000 cells/mL), acute anemia (Hb < 9 g/dL), thrombocytopenia (platelet count <50,000 cells/mL), or history of bleeding diathesis or coagulopathy, hypertrophic cardiomyopathy with or without obstruction (HOCM), echocardiographic evidence of intracardiac mass, thrombus, or vegetation, a known hypersensitivity or contraindication to aspirin, heparin, ticlopidine (Ticlid), or clopidogrel (Plavix), or sensitivity to contrast media, which cannot be adequately premedicated, excessive calcification of vessel at access site, bulky calcified aortic valve leaflets in close proximity to coronary ostia, a concomitant paravalvular leak where the surgical bioprosthesis is not securely fixed in the native annulus or is not structurally intact (e.g. wireform frame fracture), and a partially detached leaflet of the surgical bioprosthesis that in the aortic position may obstruct a coronary ostium. The safety and effectiveness have not been established for implanting the transcatheter valve inside a stented bioprosthetic valve < 21 mm (labeled size) or an unstented bioprosthetic aortic valve. Residual mean gradient may be higher in a “TAV-in-SAV” configuration than that observed following implantation of the valve inside a native aortic annulus using the same size device. Patients with elevated mean gradient post procedure should be carefully followed. It is important that the manufacturer, model and size of the preexisting surgical bioprosthetic aortic valve be determined, so that the appropriate valve can be implanted and a prosthesis-patient mismatch be avoided. Additionally, pre-procedure imaging modalities must be employed to make as accurate a determination of the internal orifice as possible.

Potential Adverse Events: Potential risks associated with the overall procedure including potential access complications associated with standard cardiac catheterization, balloon valvuloplasty, the potential risks of conscious sedation and/or general anesthesia, and the use of angiography: death; stroke/transient ischemic attack, clusters or neurological deficit; paralysis; permanent disability; respiratory insufficiency or respiratory failure; hemorrhage requiring transfusion or intervention; cardiovascular injury including perforation or dissection of vessels, ventricle, myocardium or valvular structures that may require intervention; pericardial effusion or cardiac tamponade; embolization including air, calcific valve material or thrombus; infection including septicemia and endocarditis; heart failure; myocardial infarction; renal insufficiency or renal failure; conduction system defect which may require a permanent pacemaker; arrhythmia; retroperitoneal bleed; Arteriovenous (AV) fistula or pseudoaneurysm; reoperation; ischemia or nerve injury; restenosis; pulmonary edema; pleural effusion; bleeding; anemia; abnormal lab values (including electrolyte imbalance); hypertension or hypotension; allergic reaction to anesthesia, contrast media, or device materials; hematoma; syncope; pain or changes at the access site; exercise intolerance or weakness; inflammation; angina; heart murmur; fever. Additional potential risks associated with the use of the valve, delivery system, and/or accessories include: cardiac arrest; cardiogenic shock; emergency cardiac surgery; cardiac failure or low cardiac output; coronary flow obstruction/transvalvular flow disturbance; device thrombosis requiring intervention; valve thrombosis; device embolization; device migration or malposition requiring intervention; valve deployment in unintended location; valve stenosis; structural valve deterioration (wear, fracture, calcification, leaflet tear/tearing from the stent posts, leaflet retraction, suture line disruption of components of a prosthetic valve, thickening, stenosis); device degeneration; paravalvular or transvalvular leak; valve regurgitation; hemolysis; device explants; nonstructural dysfunction; mechanical failure of delivery system, and/or accessories; non-emergent reoperation.

Ascendra+ INTRODUCER SHEATH SET

Indications: The Ascendra+ introducer sheath set is indicated for the introduction and removal of devices used with the Edwards SAPIEN XT transcatheter heart valve.

Contraindications: No known contraindications.

Warnings: The devices are designed, intended, and distributed for single use only. Do not resterilize or reuse the devices. There are no data to support the sterility, nonpyrogenicity, and functionality of the devices after reprocessing. Do not mishandle the device or use it if the packaging or any components are not sterile, have been opened or are damaged (e.g. kinked or stretched), or the expiration date has elapsed. Should not be used in patients with left ventricular aneurysm. The Ascendra+ introducer sheath set must be used with a 0.035” guidewire.

Precautions: No known precautions.

Potential Adverse Events: Complications associated with cardiac surgical intervention and use of angiography include, but are not limited to, allergic reaction to anesthesia or to contrast media, injury including myocardial injury, thrombus formation, and plaque dislodgement which may result in myocardial infarction, arrhythmia, stroke, and/or death. Reference the Edwards SAPIEN XT transcatheter heart valve with the Ascendra+ delivery system Instructions for Use for a full list of potential adverse events.

EDWARDS CRIMPER

Indications: The Edwards crimper is indicated for use in preparing the Edwards SAPIEN XT transcatheter heart valve for implantation.

Contraindications: No known contraindications.

Warnings: The device is designed, intended, and distributed for single use only. Do not resterilize or reuse the device. There are no data to support the sterility, nonpyrogenicity, and functionality of the device after reprocessing. Do not mishandle the device. Do not use the device if the packaging or any components are not sterile, have been opened or are damaged, or the expiration date has elapsed.

Precautions: For special considerations associated with the use of this device prior to valve implantation, refer to the SAPIEN XT transcatheter heart valve Instructions for Use.

Potential Adverse Events: No known potential adverse events.

CAUTION: Federal (United States) law restricts these devices to sale by or on the order of a physician. See instructions for use for full prescribing information, including indications, contraindications, warnings, precautions and adverse events.