Background
Valvular Aortic Stenosis
Aortic stenosis (AS) is a decrease in the effective area of the aortic valve leading to increased resistance to the flow of blood across the valve.[1,2] It is relatively common in the elderly with a prevalence between 4% and 5% among people over the age of 75 years.[3,4] The disease tends to progress slowly until symptoms occur.[5–7] The cardinal symptoms of aortic stenosis are angina, congestive heart failure, and syncope. Classically, these occur during exercise because the left ventricle is unable to push sufficient blood across the stenotic valve to meet the demands of the heart and the rest of the body. Surgery is indicated once someone becomes symptomatic because average survival without surgery is only two to three years.[2,8,9]
The signs of aortic stenosis on physical exam include a systolic murmur, usually loudest at the right upper sternal border, that peaks late and radiates to the right carotid artery.[10] The carotid artery pulse is classically parvus et tardus: weak and late. Finally the second heart sound may be reduced in intensity.
There are three main forms of aortic valve disease: congenital abnormalities, such as a bicuspid valve that leads to premature calcification; calcification of the normal trileaflet valve; and rheumatic valve disease. In the United States about 10% of aortic stenosis is caused by rheumatic disease and the remainder by calcification of a unicuspid, bicuspid, or normal trileaflet valve.[11–14] Calcific aortic valve disease is characterized by progressive aortic valve leaflet thickening and calcification that results in a valve that does not fully open and thus partially obstructs the flow of blood from the left ventricle into the aorta during systole.
The normal aortic valve area when open is between 3 cm2 and 4 cm2. There is no significant obstruction to flow until the valve area has decreased by 50%. As the valve narrows, the velocity of blood crossing the valve increases to compensate. The degree of stenosis is usually assessed by measuring the jet velocity with Doppler echocardiography. The normal aortic jet velocity is less than 2.5 m/sec. Symptoms usually do not occur in patients until the aortic jet velocity is greater than 4.0 m/sec and the valve area is less than 1.0 cm2. The ACC/AHA guidelines define the degree of aortic stenosis as mild, moderate, or severe based on aortic jet velocity, the mean pressure gradient across the valve, and the valve area (see Table 1).[8]
Some patients with severe AS remain asymptomatic while others with moderate stenosis develop symptoms. The decision to undergo surgery is complex and is based primarily on the development of symptoms and not the valve area, pressure gradient or jet velocity.[8]
Surgical Aortic Valve Replacement
Once someone with aortic stenosis becomes symptomatic, they are usually referred for surgery. Indications for surgery include symptomatic severe aortic stenosis, severe aortic stenosis in someone undergoing coronary artery bypass grafting or other open heart surgery, and severe aortic stenosis in someone with a left ventricular ejection fraction of less than 50%.[8] Surgical aortic valve replacement is associated with a significant risk of operative mortality, defined as any death within 30 days of the surgery. The operative mortality is commonly reported to be between 3% and 7%,[15] but has been decreasing over time despite an increase in the average age and operative risk of patients.[16,17] In the Society for Thoracic Surgeons National Cardiac Surgery Database operative mortality for isolated aortic valve replacement decreased from 3.4% in 1997 to 2.6% in 2006 while the predicted mortality increased from 2.8% to 3.2% and the average age increased from 66 years to 68 years.[16] The incidence of stroke also decreased from 1.7% to 1.3%.[16] The improvements were largest in the oldest patients. For example, for patients 85 to 89 years old, operative mortality fell from 7.8% to 4.1% and the stroke rate decreased from 4.1% to 2.4%.[16] These numbers represent reasonable benchmarks that novel therapeutic approaches need to match at a minimum.
Patients with symptomatic aortic stenosis are generally elderly and often have other significant medical illnesses putting them at high risk for perioperative complications including death. There are two risk scores that are widely used to assess patient's risk prior to surgery. The European System for Cardiac Operation Risk Evaluation (EuroSCORE) is widely used in Europe. It was developed based on 19,000 cardiac surgeries performed in Europe in 1995.[18,19] A more precise version, the logistic EuroSCORE is now more widely used.[20] It calculates the predicted operative mortality for a patient undergoing cardiac surgery. However recent studies suggest that it over-predicts the risk of death in patients undergoing valve surgery.[21–24]
The Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score was developed from a large US National database in 1994.[25–27] Similar to the EuroSCORE, it uses a large number of risk factors to predict the risk of death within 30 days of cardiac surgery. Recent validation studies suggest that it may predict the risk from isolated valve surgery more accurately than the EuroSCORE.[28–30]
Despite the poor prognosis without valve replacement and the relatively good outcomes from surgical aortic valve replacement, between 30% and 40% of patients with symptomatic aortic stenosis do not undergo valve replacement.[31,32] Even with the EuroSCORE and the STS score, there are no clear guidelines defining which patients are inoperable. However, the majority of patients with severe aortic stenosis (AS) who do not undergo surgery are determined to have co-morbidities or an overall risk for poor outcomes that makes them inoperable. Transcatheter aortic valve replacement is a potential life-saver for these patients.
Transcatheter Aortic Valve Replacement (TAVR)
Transscatheter aortic valve replacement is a novel way to replace a diseased aortic valve without a median sternotomy. The first human TAVR was performed by Dr. Cribier in 2002.[33] There have been three generations of the Cribier-Edwards SAPIEN valve. The only valve that has FDA approval is the Edwards SAPIEN valve with the Retroflex3 system. It is a trileaflet valve made from bovine pericardium in a stainless steel frame that is designed to be expanded by a balloon.
The other valve under current investigation, but not yet approved by the FDA, is the Medtronic CoreValve. It also has gone through three generations of design improvements. The current generation CoreValve is a trileaflet valve made from porcine pericardium in a self-expanding nitinol frame.
A multidisciplinary team including both interventional cardiologists and cardiac surgeons evaluate patients with aortic stenosis to decide whether the patient should receive a surgical aortic valve replacement, TAVR, or be treated medically. Patients eligible for TAVR require imaging to precisely measure the size of the aortic annulus in order to determine the correct transcatheter valve size. The iliofemoral arterial system is evaluated by angiography, most commonly using CT angiography, to document the extent of atherosclerotic disease in the peripheral vasculature. The transfemoral approach is the preferred route for TAVR, but other approaches can be used if the iliofemoral system is narrowed and heavily calcified. The transapical approach, which is the next most commonly used approach, requires a left lateral thoracotomy and direct puncture of the left ventricular apex. Other approaches include the transaortic, which requires a sternotomy and the subclavian, which requires a surgical cutdown to the left subclavian artery.
Because of the possible need to convert to an open procedure, TAVR is usually performed in a hybrid catheterization laboratory/operating room, although some institutions perform the procedure in a regular catheterization laboratory that has rapid access to an operating room. The patient is anticoagulated using heparin and the physician threads a catheter across the aortic valve and performs balloon aortic valvuloplasty. The physician then positions the prosthetic valve and expands it by inflating a balloon during rapid ventricular pacing, which is done to temporarily minimize cardiac output and prevent valve embolization. Two videos describing the procedure are available on the New England Journal of Medicine website: https://www.nejm.org/doi/full/10.1056/NEJMoa1008232. After implantation of the valve, patients are maintained on dual anti-platelet therapy for at least six months.
The primary benefit of TAVR is the ability to treat AS in patients who would otherwise be ineligible for surgical valve replacement. It may also be useful for patients at high surgical risk. Potential harms include the need for conversion to an open procedure, perioperative death, MI, stroke, bleeding, valve embolization, aortic regurgitation, heart block that requires a permanent pacemaker, renal failure, pulmonary failure, and major vascular complications such as cardiac perforation or arterial dissection. Potential long term harms include death, stroke, valve failure or clotting, and endocarditis.
CTAF © 2012 California Technology Assessment Forum
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