Transcatheter aortic valve implantation (TAVI; also known as transcatheter aortic valve replacement or TAVR) is a potential alternative treatment for patients with severe aortic stenosis. Many patients with aortic stenosis are very elderly and/or have multiple medical comorbidities, thus indicating a high, often prohibitive, risk for surgery. This procedure is being evaluated as an alternative to open surgery for high-risk patients with aortic stenosis and as an alternative to nonsurgical therapy for patients with a prohibitive risk for surgery.
Aortic stenosis. Aortic stenosis is defined as narrowing of the aortic valve opening, resulting in obstruction of blood flow from the left ventricle into the ascending aorta. Progressive calcification of the aortic valve is the most common etiology in North America and Europe, while rheumatic fever is the most common etiology in developing countries. (1) Congenital abnormalities of the aortic valve, most commonly a bicuspid valve, increase the risk for aortic stenosis, but aortic stenosis can also occur in a normal aortic valve. Risk factors for calcification of a congenitally normal valve mirror those for atherosclerotic vascular disease, including advanced age, male gender, smoking, hypertension, and hyperlipidemia. (1) Thus, the pathogenesis of calcific aortic stenosis is thought to be similar to that of atherosclerosis, i.e., deposition of atherogenic lipids and infiltration of inflammatory cells, followed by progressive calcification.
The natural history of aortic stenosis involves a long asymptomatic period, with slowly progressive narrowing of the valve until the stenosis reaches the severe stage. At this time, symptoms of dyspnea, chest pain, and/or dizziness/syncope often occur and the disorder progresses rapidly. Treatment of aortic stenosis is primarily surgical, involving replacement of the diseased valve with a bio-prosthetic or mechanical valve by open heart surgery.
Burden of illness. Aortic stenosis is a relatively common disorder of elderly patients and is the most common acquired valve disorder in the U.S. Approximately 2-4% of individuals older than 65 years of age have evidence of significant aortic stenosis, (1) increasing up to 8% of individuals by age 85 years. (2) In the Helsinki Aging Study, a population-based study of 501 patients aged 75-86 years, the prevalence of severe aortic stenosis by echocardiography was estimated to be 2.9%. (3) In the U.S., more than 50,000 aortic valve replacements are performed annually due to severe aortic stenosis.
Aortic stenosis does not cause substantial morbidity or mortality when the disease is mild or moderate in severity. By the time it reaches the severe stage, there is an untreated mortality rate of approximately 50% within 2 years. (4) Open surgical repair is an effective treatment for reversing aortic stenosis, and artificial valves have demonstrated good durability for periods of up to 20 years. (4) However, these benefits are accompanied by a perioperative mortality of approximately 3-4% and substantial morbidity, (4) both of which increase with advancing age.
Unmet needs. Many patients with severe, symptomatic aortic stenosis are poor operative candidates. Approximately 30% of patients presenting with severe aortic stenosis do not undergo open surgery due to factors such as advanced age, advanced left ventricular dysfunction, or multiple medical comorbidities. (5) For patients who are not surgical candidates, medical therapy can partially alleviate the symptoms of aortic stenosis but does not affect the underlying disease progression. Percutaneous balloon valvuloplasty can be performed, but this procedure has less than optimal outcomes. (6) Balloon valvuloplasty can improve symptoms and increase flow across the stenotic valve but is associated with high rates of complications such as stroke, myocardial infarction (MI), and aortic regurgitation. In addition, restenosis can occur rapidly, and there is no improvement in mortality. As a result, there is a large unmet need for less invasive treatments for aortic stenosis in patients who are at increased risk for open surgery.
Transcatheter aortic valve implantation (TAVI). TAVI has been developed in response to this unmet need and is intended as an alternative treatment for patients in whom surgery is not an option due to prohibitive surgical risk or for patients who are at high risk for open surgery. The procedure is performed percutaneously, most often through the transfemoral artery approach. It can also be done through the subclavian artery approach and transapically using mediastinoscopy. Balloon valvuloplasty is first performed in order to open up the stenotic area. This is followed by passage of a bioprosthetic artificial valve across the native aortic valve. The valve is initially compressed to allow passage across the native valve and is then expanded and secured to the underlying aortic-valve annulus. The procedure is performed on the beating heart without the need for cardiopulmonary bypass.
There are at least two transcatheter aortic valve devices being tested. The Edwards SAPIEN heart-valve system™ (Edwards Lifesciences, Irvine, CA) is a tri-leaflet bioprosthetic porcine valve that is contained within a stainless steel frame. This device has been commercially available in Europe since 2007 but has not yet received U.S. Food and Drug Administration (FDA) approval in the U.S. There is currently a next generation version of this valve in testing, called the SAPIEN XT™ (Edwards Lifesciences, Irvine, CA), which has been redesigned with the intention of reducing procedural complications.
The Medtronic CoreValve ReValving System™ is a second transcatheter valve system under testing. This device is a porcine bioprosthetic valve that is sewn within a self-expanding nitinol frame. It is inserted via the transfemoral artery approach and has also been inserted via the subclavian artery approach. This device has also been approved for use in Europe since 2007 but has not yet received FDA approval in the U.S.
The Sapien Transcatheter Heart Valve System™ (Edwards LifeSciences, Irvine, CA) received original FDA approval in November 2011 for patients with severe aortic stenosis who are not eligible for open-heart procedures and have a calcified aortic annulus. In 2012, an additional FDA premarket approval (PMA) was granted for the Edwards SAPIEN™ transcatheter heart valve Model 9000TFX (Edwards LifeSciences, Irvine, CA) with expanded indications for use. (7) Approval was granted for both the transfemoral and transapical approach. For the transfemoral approach, patient indications were broadened to include patients who are at high risk for open surgery. For the transapical approach, approval was granted for patients who are at high risk for open surgery.