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In the elderly high-risk patients in the PARTNER (Placement of Aortic Transcatheter Valve) trial who were treated medically (Cohort B), the survival at 1 year was only 50%. 15 The natural history of AS has changed since the publication of the seminal paper by Morrow and colleagues in 1968. The original data were derived largely from patients with rheumatic AS or AS due to a bicuspid aortic valve, with an average age of death of 63 years. On the contrary, patients being considered for TAVR on a trileaflet valve present much later in life, typically in their late 70s or older, and have dominantly fibrocalcific AS. Although now occurring later in life, the onset of symptoms still heralds a rapid decline with medical therapy alone. Diagnosis:Echocardiography Versus Catheterization Assessment of the severity of stenosis does not differ in TAVR patients compared with the general AS population, and decisions should therefore be based upon established guidelines. Although invasive cardiac catheterization has historically been the standard for quantification of AS, this function has been largely replaced by echocardiography. Echocardiographic diagnosis is made by the observation of a calcified valve with restricted leaflet opening by two dimensional (2D) echocardiography with quantification of the peak and mean AV gradient made by applying the simplified Bernoulli equation (Dp ¼ 4v2 ) to the maximal velocity recorded through the aortic valve by continuous-wave Doppler. Multiple imaging windows (apical 4-chamber and long-axis, right parasternal, suprasternal notch, and subcostal views) should be obtained to assure acquisition of the maximal velocity and to avoid angle-related errors. Although aortic valve area (AVA) can be measured by planimetry, it is more accurately assessed by application of the continuity equation, using pulsed-wave Doppler in the left ventricular outflow tract (LVOT) and continuouswave Doppler across the valve. Severe stenosis is defined in the guidelines as a peak velocity>4.0 m/s (corresponding to a peak gradient of 64 mm Hg), a mean gradient>40 mm Hg, OR valve area<1.0 cm2 when LV systolic function is normal. To account for patient size, the valve area is often indexed to body surface area, with 0.6 cm2 /m2 considered to be the threshold for severe AS. An important exception is when the gradient suggests less severe stenosis than the valve area, most commonly due to low stroke volume, either in dilated ventricles with low ejection fraction (EF) or small ventricles with normal EF. In this setting, a dobutamine stress study (maximum stress dose 20 mcg/kg/min), may be helpful. If the maximum jet velocity rises over 4 m/s with the dobutamine-induced increase in stroke volume whereas the AVA remains less than 1.0 cm2 , then the valve is truly severely stenotic. On the other hand, if stroke volume increases with little rise in gradient (causing valve area to increase substantially), then the AS is only mild to moderate in severity, and the LV dysfunction is due to causes other than AS. Occasionally, the AVA appears larger than the elevated gradient would suggest, usually due to elevated stroke volume from aortic regurgitation (AR), anemia, fever, or hyperthyroidism. Sometimes, though, it reflects a technical error in applying the continuity equation, when the blood accelerates within the LVOT due to an upper septal bulge, which may result in an overestimation of valve area. To avoid this, one can try to measure the LVOT area at the point of maximal velocity, though the geometry is often quite distorted in this region, making estimation of the LVOTarea difficult. Alternatively, one can use the LV stroke volume (from 2D or three-dimensional [3D] measurements of the LV, ideally with contrast infusion) or right ventricular (RV) stroke volume (from RVoutflow tract) as the input into the continuity equation. Dividing this stroke volume by the time velocity integral of the AV continuous-wave Doppler will also yield the AVA, independent of any distortion in the LVOT. Despite the convenience and wide-spread applicability of transthoracic echocardiography (TTE), there are occasions when invasive measurements are needed, such as in patients with a discrepancy between clinical and echocardiographic assessments. In such cases, catheterization should generally be performed with dual catheters, 1 placed in the LV, the other in the proximal aorta to obtain simultaneous pressure measurements and obtain the most accurate assessment of the gradient. Infusion of dobutamine may allow assessment of low-output, low-gradient AS in the catheterization laboratory. Other adjunctive testing used in quantifying AS includes transesophageal echocardiography (TEE), CT scanning (dynamic or gated during systole), and CMR. Stress Testing The presence or absence of symptoms should guide the management of AS patients, yet in many cases, this important clinical benchmark is difficult to establish, owing to the subjective nature of the symptoms and comorbid conditions such as chronic lung disease in this patient population. In general, stress testing is contraindicated when symptoms are present because of the potential for complications in these patients. However, in patients with equivocal symptoms, stress testing, and in particular stress echocardiography, can be very helpful. Simple determination of functional capacity may help show limitations of which a patient may be unaware. Isolated echocardiographic (ECG) changes during the stress test without symptoms or change in blood pressure should not be interpreted as a positive indicator of severe AS. Other potential markers for AS severity include signs of LV dysfunction on exercise echo or a rise in left atrial or right ventricular pressure. Special Considerations :Symptom Status With severe, symptomatic, calcific AS, AVR is the only effective treatment that improves symptoms and prolongs survival.30,31 These results are partly dependent on LV function. In the setting of LV dysfunction caused by afterload mismatch, survival is still improved, although improvement in LV function and resolution of symptoms might be incomplete after AVR. Age itself is a risk factor for adverse outcome, but it is not a contraindication to AVR even in the very elderly.Associated Coronary Artery Disease In patients with moderate AS, who are undergoing coronary artery bypass graft surgery (CABG), AVR should be performed at the time of revascularization irrespective of symptoms related to moderate AS. There are no data to support performing AVR for mild AS at the time of CABG. Patients undergoing surgical AVR with significant stenoses (>50% to 70% stenosis) in major coronary arteries should be treated with concomitant CABG.