The role of echocardiography in the evaluation and management of aortic stenosis in the older adult

International Journal of Cardiology 155 (2012) 39–48

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International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d

Review

The role of echocardiography in the evaluation and management of aortic stenosis in the older adult Fadi G. Hage a,b, Ayodeji Adegunsoye a, Mallika Mundkur a, Navin C. Nanda a,⁎ a b

Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL, USA Section of Cardiology, Birmingham Veteran's Administration Medical Center, Birmingham, AL, USA

a r t i c l e

i n f o

Article history: Received 1 December 2010 Accepted 1 January 2011 Available online 12 March 2011 Keywords: Aortic stenosis Transthoracic real time live 3-dimensional echocardiography Older adults

a b s t r a c t Aortic stenosis is currently the most predominant valvular pathology in older adults. Signs and symptoms of aortic stenosis in this age-group may be difficult to recognize due to the decreased activity associated with aging and attribution of symptoms to other conditions. Echocardiography can be very helpful in the assessment of valvular structure and real time hemodynamic evaluation as well as in the progression of the disease over time. Unprecedented advances in echocardiography, including real time three-dimensional echocardiography, facilitate a comprehensive assessment of this condition and help in the decision-making process. Recent innovations in the percutaneous treatment of valvular diseases promise a revolution in the treatment of aortic stenosis especially in older adults. © 2011 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Major advances in the diagnosis and management of valvular heart diseases over the last decades have led to a rise in the prevalence and increased life expectancy of these conditions in all age groups. [1] Aortic valve stenosis (AS) is a disease of aging and therefore its contribution to morbidity and mortality is magnified in older adults. One in four individuals over the age of 65 years (and one in two over 80 years) in the general population have sclerosis of the aortic valve. [2] Moderate to severe AS is present in one in ten adults aged 80 years and older. Calcific AS is the most common indication for valve replacement surgery, and the second most common indication for cardiac surgery, after coronary artery bypass grafting, in older adults [3]. Challenges routinely encountered in the evaluation of AS in the older population are related to the difficultly in recognition of symptoms due to age-associated decrease in activity, symptom attribution to other conditions that are common in the elderly, complexity of associated multiple co-morbidities and variations in individual functional capacity [4,5]. Echocardiography allows for the noninvasive assessment of valvular structure and the real time evaluation of its hemodynamic consequences and is endorsed by the current guidelines as the diagnostic test of choice for the assessment of AS [1]. In addition to 2-dimensional transthoracic (2DTTE) and transesophageal (2DTEE) echocardiography, the utilization of real time three-dimensional (3D) TTE and 3DTEE facilitate ⁎ Correspondence author at: University of Alabama at Birmingham, Heart Station, SWB/S102, 619 19th Street South, Birmingham, AL 35249, USA. Fax: + 1 205 934 6747. E-mail address: [email protected] (N.C. Nanda). 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.01.080

spatial recognition of both anatomy and function and allow for the direct assessment of stenosis severity [6]. Thus the use of echocardiographic imaging can be helpful in the diagnosis of AS in older adults and in the decision-making process in this particular patient population. 2. Pathogenesis The most common cause of AS in older adults is the calcification of the aortic valve leaflets. This process usually starts with aortic valve sclerosis which does not limit flow through the aortic orifice but as the disease advances over decades, the valve leaflets become more rigid, lose their mobility and fuse together to obstruct flow. Thus, the natural history of the disease is that of progression from sclerosis to stenosis. Once AS develops, the average rate of reduction in the aortic valvular orifice is ~ 0.1 cm2/year. This progression accelerates with age and studies have shown remarkably faster deterioration in octogenarians with mild to moderate AS, as their aortic valve area diminishes twice as fast as matched controls twenty years younger [7]. A less common cause of AS in the elderly is a bicuspid aortic valve, a common congenital abnormality present in 1–2% of the population, that often presents in younger individuals and rarely stays asymptomatic until affected individuals are over their sixth decade [8]. Although AS has been considered a degenerative ‘wear and tear’ disease in the past, it is now known that active inflammation and processes that are closely linked to vascular atherosclerosis contribute to the progression from aortic sclerosis to stenosis by means of valvular calcification. Monocyte/macrophage infiltration and T-cell activation seem to be key elements in this process as well as the efflux of oxidized lipids into the lesion which results in the formation of

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foam cells. The lipids implicated in this process closely resemble those involved in vascular atherogenesis and include low density lipoprotein as well as lipoprotein a. These lipids can enhance the inflammatory activity in the lesion and induce mineralization. Other systems that participate in this process include transforming growth factor β, tumor necrosis factor α, the renin–angiotensin–aldosterone system, nuclear factor-κB and others. In addition to the pathophysiological similarity to atherosclerosis, AS and coronary disease share many clinical risk factors such as diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and tobacco use [9]. 3. Anatomy and hemodynamics Understanding the anatomy of the normal aortic valve and the hemodynamic derangements that result from its restriction of motion is crucial in AS. The normal aortic valve is formed by three crescent shaped thin leaflets arranged at the terminal aspect of the left ventricular (LV) outflow tract (OT) and laterally attached to its walls [10]. The symmetrical arrangement of these leaflets result in the formation of a central opening in systole, that normally measures 3–4 cm2, and a closure in diastole thus allowing normal blood flow during cardiac contracture while preventing the backflow of blood from the aorta when the heart is relaxed. The aortic valve, located anteriorly in the chest, is in an excellent position for examination by transthoracic and transesophageal echocardiography [11]. As the aortic valve orifice area becomes smaller with AS progression, the velocity of blood flow in the orifice accelerates and this can be detected by flow Doppler measure-

ments as will be detailed later in the chapter. The evaluation of the anatomic structure of the valve with echocardiography can also be extremely useful and this spatial visualization can be done better with 3DTTE (Fig. 1). 4. Signs and symptoms AS may remain asymptomatic for years and the occurrence of symptoms, usually in the sixth to eighth decades, indicate that the stenosis is severe and is the main guide in patient management [12]. The classic symptoms of severe AS include angina, syncope, and dyspnea, all of which are typically with exertion. Occasionally gastrointestinal bleeding is seen secondary to arteriovenous malformations, platelet dysfunction, and defective coagulation in what is termed Heyde syndrome [13–15]. In older adults, symptoms are often delayed due to the decreased activity levels and the attribution of symptoms to other conditions. Since AS in older adults is associated with increased risk for myocardial infarction and cardiovascular death, special attention should be focused on the elicitation of symptoms and on easy fatigability even in the absence of exertional symptoms [16]. The disease continuum is mostly asymptomatic until the restriction on forward flow overcomes the compensatory mechanisms. Angina in severe AS is due to supply–demand mismatch caused by a combination of LV hypertrophy, increased afterload, increased wall strain and the excessive compression of the coronary arteries. Exertional syncope is secondary to decreased cerebral perfusion

Fig. 1. Live 3-dimensional transthoracic echocardiography for assessment of aortic valve structure. (A, B) The aortic valve appears to be bicuspid on two-dimensional transthoracic echocardiography. (C,D) Live 3-dimensional transthoracic echocardiography shows the valve to be quadricuspid with four numbered leaflets clearly visualized. The patient underwent aortic valve replacement for severe aortic regurgitation due to noncoaptation of the valve leaflets and was confirmed to have a quadricuspid aortic valve. LA = left atrium, RA = right atrium, RV = right ventricle, TV = tricuspid valve. (Reproduced with permission from Burri MV, Nanda NC, Singh A, Panwar SR: Live/real time three-dimensional transthoracic echocardiographic identification of quadricuspid aortic valve. Echocardiography 2007;24:653–655).

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caused by the vasodialation accompanying exertion and the inability to increase cardiac output caused by the fixed LVOT obstruction. Dyspnea is a late presenting symptom of severe AS caused by the failure of the LV to compensate for the outflow obstruction. On physical examination, a late peaking systolic crescendo– decrescendo murmur usually heard maximally at the base of the heart characterizes severe AS. Older adults exhibit certain variations to this characteristic pattern. The occurrence of heart failure and chronic lung disease common in this population results in a significant reduction in the intensity of the murmur while pure aortic sclerosis without stenosis may present with an apical systolic high pitched murmur (Gallvardin phenomenon). The carotid ‘pulsus parvus et tardus’, a slow and delayed carotid pressure wave upstroke resulting from obstructed flow across the aortic valve, a hallmark of AS in younger individuals is typically absent in older adults who have stiff non-compliant vasculature due to atherosclerosis. Progressive valve calcification with increasing age results in absence of the aortic component of the second heart sound and the occurrence of a left ventricular heave and S4 gallop is non-specific due to the prevalence of co-existing hypertension in this patient population. 5. Echocardiographic evaluation

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malalignment of the beam with the flow across the valve will lead to underestimation of the velocity, and therefore of the severity of AS, in a manner that is dependent on the angle of malalignment. Since the stenotic jet is a 3D structure, the 2D Doppler cursor may appear to be in the jet when it is not picking up the true jet core velocity (Fig. 2). In order to minimize this source of error the highest velocity detected from multiple views should be assumed to correspond to the proper alignment being cautious that the Doppler signal is not being polluted by flow across a different valve such as mitral regurgitation [21]. One of the more common sources of error in determining the aortic valve area is related to the inaccuracy of measuring the LVOT diameter. This is especially difficult in older adults who often have annular calcification that further complicates this measurement. Since the LVOT diameter is squared in the calculation of aortic valve area, even minor variations in measurement will lead to large errors in the area. Particular attention to this point is warranted when evaluating the progression of severity of stenosis in an individual patient since large factitious variations in the calculated valve area can be due to erroneous measurements of the diameter which should not change significantly in adult patients [18]. In an attempt to adjust for these errors some authorities advocate the use of the dimensionless index, the ratio of the velocity across the LVOT to that across the aortic valve, which completely eliminates the area of the LVOT from the equation [18].

Since the classical signs and symptoms may be limited for gauging the severity of AS in older adults, greater emphasis is placed on echocardiography in this population. 2DTTE can show the morphological changes of severe AS such as leaflet calcification, thickening and deformities. The valve leaflets appear domed on 2DTTE and have less mobility and there is diminished leaflet separation in systole [17]. 2DTTE can also be quite helpful for assessing the effects of AS on the LV. Due to the pressure overload placed on the LV by the stenotic valve, the LV hypertrophies and ultimately the myocardium becomes dysfunctional and fails. Occasionally, when a discrete orifice is demonstrated, the valve area can be directly measured with planimetry in a manner similar to the assessment of mitral stenosis. However, this method is unreliable in the case of AS because of the inability to tell whether the plane of imaging is at the leaflet tips where maximum stenosis occurs and that it is parallel to the orifice. 5.1. 2DTTE/Doppler Determining the severity of AS with 2DTTE therefore mostly depends on Doppler interrogation. As the aortic valve orifice becomes more restrictive, the velocity of blood flow that traverses the orifice increases. Doppler can be used to determine the velocity of blood flow and, using the Bernoulli equation, the pressure gradient across the aortic valve. The principle of continuity of flow that states that blood flow across the aortic valve is equivalent to that across the LVOT can be used to determine the area of the aortic valve by measuring the velocities across the LVOT and the aortic valve and the diameter of the LVOT [18]. Although these measurements have been validated, overestimation or underestimation of the severity of stenosis does occur. One of the assumptions inherent in the use of the continuity equation is that the LVOT diameter and the flow across the LVOT are measured at the same place. However, this is difficult to establish since these measurements are performed in different echocardiographic views. Another limitation is that continuous wave Doppler detects the fastest velocity along its interrogation line but is not equipped to determine the level of flow obstruction. This can be important in patients with associated subaortic or supra-aortic obstruction and especially in those with serial flow obstructing lesions. A major source of discrepancy between pressure gradients determined by the Doppler technique and those determined by invasive methods is attributed to the alignment of the Doppler interrogation beam [19,20]. Interrogating in the flow acceleration area can overestimate the velocity due to flow turbulence, while

Fig. 2. Because a stenotic jet consists of a small central region or core of high velocity and a larger outer region of lower velocity, the continuous wave Doppler cursor must be positioned in the jet core in addition to being aligned parallel to the jet direction to measure the maximum jet velocity. The 3D structure of the jet may cause the continuous wave cursor to appear to be positioned correctly in the jet while, in reality, the cursor may not be placed properly in the jet core. Therefore, after the initial alignment of the continuous wave cursor in the visualized jet, minimal transducer angulations still are required to interrogate the jet core, which may be in the azimuthal plane. Failure to interrogate the core results in an underestimation of the peak transvalvular velocity and thus the severity of the stenotic lesion. In this illustration, the aortic stenosis (AS) jet is shown to consist of a central core, which has the highest velocity, and this central core is surrounded by an outer region of lower velocity flows. The highest velocity thus is obtained if the continuous wave Doppler cursor is aligned parallel to the core of the jet (cursor 2), while lower velocities are recorded if the cursor is positioned outside the core (cursors 1, 3, 4, 5). (Reproduced with permission from Nanda NC (editor). Atlas of Color Doppler Echocardiography. Philadelphia: Lea & Febiger; 1989:112).

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Another source of error that is also more common in older adults is related to the phenomenon of pressure recovery. Pressure recovery can lead to the overestimation of the severity of AS when measured by Doppler (as compared to invasive maneuvers) due to the conversion of kinetic energy to potential energy downstream from the stenosed valve. This effect is known to be exaggerated in individuals with tubular stenoses, a narrow width of the ascending aorta (b3 cm), or a small diameter of the LVOT (≤2 cm) [22–25]. These and other sources of error can lead to over- or under-estimation of the severity of AS when determined indirectly by Doppler measurements. It is important to note that the ‘gold standard’ assessment of AS severity using invasive measurements and the Gorlin formula is also susceptible to multiple sources of error especially in patients with low-flow states [26–28]. In addition, cardiac catheterization is invasive and serious complications are more common with advancing age [29,30]. The risk of fatal complications doubles when the aortic valve is crossed during cardiac catheterization [31]. The occurrence of focal acute cerebral embolic events in response to retrograde crossing of the aortic valve is not trivial and has been shown to be more than 20% by magnetic resonance imaging in an older population [32].

infinite possible levels and angulations to allow for a full assessment of the aortic valve structure (Fig. 3).

5.2. 2DTEE 2DTEE can be used for assessing the severity of AS. In order to visualize the aortic valve in short axis, the probe is withdrawn to the supravalvular aorta where no leaflets are visualized, then very gradually advanced till the leaflets first appear. The orifice is then planimetered at this point (flow-limiting tip of the stenosed AV leaflets). 2DTEE has been shown to be useful for this purpose especially in patients with limited transthoracic windows but it has some significant limitations [33]. The superior image resolution seen with 2DTEE allows for better visualization of the valve structures as compared to 2DTTE but the images in 2D lack depth perception and require mental reconstruction of the spatial anatomy. This is particularly important in older adults because of the prevalence of severely calcified valvular cusps which cause acoustic shadowing and interfere with visualization using 2DTEE in addition to anatomical variations caused by a dilated or obliquely placed aorta [33]. In older adults the prevalence of severely calcified valvular cusps which cause acoustic shadowing and interfere with visualization using 2DTEE in addition to anatomical variations caused by a dilated or obliquely placed aorta is increased [33]. Another limitation faced by 2DTEE is the inability to ensure that the imaging plane is aligned perpendicular to the plane of the orifice [34,35]. Since this depends on the relationship of the probe in the esophagus and the aortic root, which is fixed in a particular individual but variable from one person to another, it is technically difficult to ensure that the imaging plane is parallel to the plane of the orifice. Thus, some studies have shown good correlation of 2DTEE measured aortic orifice area with invasive measurements while others have not [33]. 5.3. 3DTTE Due to the limitations seen with 2D imaging, 3D echocardiographic imaging has been considered in the evaluation of aortic valve pathologies early on in its development [11]. The major technological advancements in the field of 3D echocardiography including the development of the full matrix-array transducer allowed for the introduction of real-time live 3D imaging using clinically available systems that are routinely utilized in everyday practice replacing older systems that relied on 3D reconstruction techniques that are time-consuming and produced imaging artifacts [6]. 3DTTE now plays an essential role in the evaluation of AS in the aging population by providing incremental information on top of routine 2DTTE [36,37]. Using 3DTTE, the whole aortic root can be included in the 3D pyramidal dataset that can then be sectioned using cropping planes at

Fig. 3. Live, real time 3D echocardiography in aortic stenosis. (A) The aortic valve (AV) is viewed in the parasternal long-axis view showing calcified leaflets. The data set then was cropped from right to the level of the flow-limiting tip of the AV leaflets (B) and rotated en face to view the very narrow aortic orifice in short axis consistent with severe stenosis (C). The patient has the so-called acquired bicuspid aortic valve because of fusion of two of the three cusps. Abbreviations: LA, left atrium; LV, left ventricle. (Reproduced with permission from Mallavarapu RK, and Nanda NC. Three-dimensional transthoracic echocardiographic assessment of aortic stenosis and regurgitation. Cardiol Clin 2007;25:327–334).

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Performing 3DTTE on top of the standard 2DTTE evaluation of AS provides anatomical assessment of stenosis severity which is more accurate than the Doppler variables. Using this technique of directly measuring the orifice area can circumvent most of the limitations of the indirect Doppler measurements (Fig. 4). Although directly measuring the aortic orifice area can be done with 2DTTE and 2DTEE using planimetry it is difficult to ensure that the imaging plane

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is through the flow-limiting orifice. After including the entire aortic valve in the 3D pyramidal dataset using 3DTTE, the aortic orifice area can be measured precisely and accurately by aligning the imaging plane exactly parallel to the aortic valve orifice in the short-axis view where it can be planimetered [38]. This provides increased confidence to the operator that the imaging plane is not slanted relative to the plane of the orifice and that the area measured is that of the flow-

Fig. 4. Live 3-dimensional transthoracic echocardiography in aortic stenosis. (A) Two-dimensional transthoracic echocardiography shows a calcified aortic valve (AV) with restricted motion consistent with stenosis. (B) Color Doppler guided continuous wave Doppler demonstrates a peak and mean gradient of 56 mm of Hg and 32 mm of Hg, respectively and the AV orifice area (AVO) was estimated to be 0.93 cm2 using the continuity equation all indicating moderate stenosis. (C,D) Live 3-dimensional transthoracic echocardiography. In C, the arrowhead points to the calcified AV with restricted motion, in long axis, while in D the arrowhead points to the AV orifice in short axis. AV orifice area measured 0.46 cm2 by planimetry indicating severe stenosis. (E) Intra-operative two-dimensional transesophageal echocardiography revealed an AVO (arrowhead) of 0.46 cm2 consistent with severe stenosis. (F) This was confirmed using an intra-operative three-dimensional transesophageal echocardiographic reconstruction which showed an AVO (arrowhead) of 0.40 cm2. Therefore, in this patient although severe AV stenosis was missed by two-dimensional transthoracic echocardiography and Doppler, it was correctly diagnosed by live threedimensional transthoracic echocardiography as subsequently confirmed by intraoperative two-and three-dimensional transesophageal echocardiography, and at surgery. (Reproduced with permission from Vengala S, et al.: Usefulness of Live Three-Dimensional Transthoracic Echocardiography in Aortic Valve Stenosis Evaluation. Am J Geriatric Cardiol 2004;13:279–284).

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orifice in the required imaging plane. The unique feature of visualizing 2D planes from a 3D dataset at any angulation has proven especially useful for the assessment of angulated orifices and domed aortic valves [38]. Another significant advantage offered by 3DTTE is its ability to accurately measure the flow limiting area in patients with serial lesions such as hypertrophic cardiomyopathy or combined valvular and supravalvular AS while Doppler is unable to do that (Fig. 5) [38,39]. Another limitation to the use of Doppler is the inability to localize the site of high velocity flow along the line of interrogation. Patients with subaortic membranous stenosis can therefore be misdiagnosed to have hypertrophic obstructive cardiomyopathy or aortic valvular stenosis [40–42]. Since invasive pressure measurements can occasionally miss the diagnosis, direct anatomic identification of the membrane is the preferred approach [42]. This can be done with 2DTEE or with 3D reconstruction of 2DTEE images which allows for a full evaluation of the lesion by systematic cropping along the LVOT to identify the site of stensis [43–46]. With live 3DTTE this can also be done non-invasively and in real time to localize the site of stenosis and the full extent of the membrane [47]. Using techniques similar to those discussed above for aortic stenosis, the narrow opening within the membrane can be viewed en face to allow for measuring the area of the orifice and anatomically determine the severity of flow obstruction without any assumptions or estimations [47,48]. In addition to its use for assessing the severity of aortic stenosis, 3DTTE can be quite useful for the evaluation of prosthetic valves after aortic valve replacement surgery (Fig. 6) [49]. Doppler gradients are infamously unreliable for the evaluation of metallic prosthetic valves and 3DTTE has been shown to provide more accurate information regarding prosthetic valve dysfunction [49,50]. 5.4. 3DTEE The recent introduction of a 3DTEE probe capable of real-time imaging, as compared to 3D reconstruction of 2DTEE images, [51] has opened a new era in 3D imaging of the aortic valve that combines the higher resolution of TEE with the capability of cropping the 3D dataset to overcome the anatomical limitations of 2DTEE (Fig. 7) [52]. The real time nature of this technology can be especially useful in the immediate postoperative period to evaluate the aortic valve prosthesis and the suture ring using high-resolution en face views while the patient is still on the operating table. Another advantage of this technique is the clarity of the images in patients with poor acoustic windows in whom 3DTTE is of limited value. 6. Management of aortic valve stenosis in older adults The management of AS in older adults is multifaceted and involves the consideration of several factors unique to this patient population. The treating physician has to consider the high prevalence of

limiting orifice. This measurement has been shown to better correlate with the aortic valve area measured intra-operatively by 3DTEE than does 2DTTE/Doppler or 2DTEE [38]. Furthermore, it is able to correctly diagnose severe aortic stenosis in patients missed by conventional Doppler measurements who are confirmed intra-operatively to have severe stenosis [38]. Therefore, 3DTTE provides an entirely noninvasive approach for the assessment of the severity of aortic stenosis that avoids the limitations of the use of Doppler and puts forward a method for reliably quantitating the area of the anatomic stenotic

Fig. 5. Live real time three-dimensional transthoracic echocardiographic assessment of combined valvar and supravalvar aortic stenosis. (A) The arrowheads point to prominent calcification at the sino-tubular junction viewed in long axis. (B) Short axis view at the sino-tubular junction shows a large orifice (arrowhead) which measured 2.5 cm2. (C) Short axis view at the level of the aortic valve (left) and immediately above it (right). The aortic valve orifice measured 1.7 cm2 by planimetry consistent with mild aortic stenosis. The arrowhead in the right panel points to sinotubular calcification protruding into the aortic lumen imaged just beyond aortic valve leaflets. AA = ascending aorta; AO = aortic root; AV = aortic valve; LA = left atrium, LV = left ventricle; MV = mitral valve; PA = pulmonary artery; PV = pulmonary valve; RA = right atrium; RV = right ventricle; RVO = right ventricular outflow tract; TEE = transesophageal echocardiography; TTE = transthoracic echocardiography; TV = tricuspid valve. (Reproduced with permission from Rajdev S, et al.: Live/Real Time Three-Dimensional Transthoracic Echocardiographic Assessment of Combined Valvar and Supravalvar Aortic Stenosis. Am J Geriatric Cardiol 2006;15:188–190).

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The guidelines advocate aortic valve replacement (AVR) once symptoms develop since this has been shown to improve survival [1]. 6.1. Surgical AVR

Fig. 6. Live/real time three-dimensional transthoracic echocardiographic assessment of St. Jude aortic prosthesis. Arrow points to severe AVR stenosis. The data set was cropped to view the prosthesis en face. (Reproduced with permission from Singh P, et al. Usefulness of Live/Real Time Three-Dimensional Transthoracic Echocardiography in Evaluation of Prosthetic Valve Function. Echocardiography 2009;26:1236–1249).

atherosclerotic vascular disease as well as other co-morbidities, multiple medical therapies, risks of anticoagulation, presence of coexisting valvular pathologies and the extent of aortic calcification [53]. The slow progressive nature of AS usually allows for the monitoring of disease severity and symptom development. Once AS becomes severe, symptoms usually develop and prognosis quickly becomes dismal.

The risks and benefits of AVR must be weighed against those of watchful waiting. The overall survival of asymptomatic patients with severe AS is identical to the general population after adjustment for age and gender. Although sudden cardiac death does occur in these patients, it is thought to be quite rare (b1%/year) in the truly asymptomatic. The peri-operative risk of death after isolated AVR is on the order of 1–4% and increases to almost 9–10% in octogenarians especially in the presence of multiple comorbidities (chronic obstructive lung disease, renal insufficiency, peripheral vascular disease, coronary artery disease) [54]. Therefore, the risk–benefit ratio would not justify early preemptive AVR in older adults prior to the development of symptoms. Nevertheless, since it is imperative to intervene quickly after the development of symptoms, some have advocated the performance of submaximal exercise stress tests in patients with unclear medical history. Although exercise stress tests are contraindicated in patients with symptomatic severe AS due to the high risk of complications, they are relatively safe in patients with asymptomatic severe AS and can provide information to guide therapy. This approach is given a recommendation class IIb in current guidelines [1]. The development of symptoms heralds poor prognosis. Classical studies have demonstrated that the average survival after the development of symptoms is 2–5 years [55]. Recent series in older populations with calcific AS confirmed the prognostic significance of symptom

Fig. 7. 3D transesophageal echocardiographic reconstruction in aortic valve stenosis. Thickened bicuspid aortic valve without significant stenosis, shown in the closed (A) and open (B) positions. (C) Severe, calcified bicuspid aortic valve stenosis. Note the transversely oriented very small aortic orifice (arrowhead). (D) Another patient with calcific severe stenosis. Note that despite severe calcification, the tricuspid morphology of the valve is evident. Abbreviations: AO, aorta; RA, right atrium; RVO, right ventricular outflow tract. (Fig. 3A, B and D are reproduced with permission from Mallavarapu RK et al.: Echocardiographic assessment of aortic stenosis in the elderly. Am J Geriatric Cardiology 2007;16:343– 348. Fig. 3C is reproduced with permission from Dod HS, et al. Three-dimensional transesophageal echocardiographic assessment of aortic valve pathology. AmJ Geriatric Cardiology 2003:12:209–13).

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development and suggested the importance of three additional predictive factors: New York Heart Association class III or IV, concurrent mitral regurgitation, and left ventricular systolic dysfunction [56]. Thus the development of symptoms in patients with severe AS is a solid indication for AVR. The criteria for referral to surgery (AVA b1.0 cm2 with either low ejection fraction or symptoms) are independent of age and are identical for older and younger patients [1,53]. Nevertheless, any decision regarding surgical intervention should take into account the patient's level of risk and benefit from the surgical procedure as well as life expectancy and the patient's personal wishes. The peri-operative risk of AVR is usually estimated at 2% in all-comers but the risk is known to increase with age. The 60-day mortality after AVR is 5.0%, 7.7% and 11% in sexagenarians, septuagenarians, and octogenarians, respectively [57–59]. Long-term mortality is 25%, 29%, and 40% for the same age groups after a mean follow-up of 5.66 years, 5.42 years, and 4.58 years, respectively [57–59]. It should be noted that the risk is not uniform in each age-group and it is not significantly higher in octogenarians who are undergoing AVR on an elective basis. The risk is much higher in older adults with a lower ejection fraction and in those undergoing repeat surgery or urgent valve replacement [60]. Other reports have estimated peri-operative mortality in octogenarians at around 8–20% with some showing higher risk in patients undergoing simultaneous coronary artery bypass grafting although this is not uniform across studies. For example, in the study by Melby et al. in octogenarians, 30-day mortality was 9%, 1-year survival 82%, and 5-year survival 56%, and performing CABG improved 30-day and long-term survival (HR, 0.7; 95% CI, 0.47 to 0.96; p=0.020) [61]. Important predictors of peri-operative mortality in this age group include chronic kidney disease, previous bypass surgery, previous myocardial infarction, previous stroke, advancing age, aortic insufficiency, and left ventricular dysfunction while predictors of long-term mortality include chronic kidney disease, diabetes mellitus, previous myocardial infarction, left ventricular dysfunction, female gender, peripheral vascular disease, and pulmonary disease [53]. Despite the increased short-term risk of AVR, older individuals have much to gain in long-term survival, function and quality of life. Octogenarians experience an improvement in symptom burden, physical ability and well being of a similar magnitude to that of younger patients at 1 year after AVR and the quality of life of survivors is comparable to the age-matched general population [1,62]. Therefore, older individuals with severe symptomatic AS should not be denied surgery based on advanced age alone. In the peri-operative evaluation prior to AVR, cardiac catheterization is indicated for the assessment of coronary artery disease using coronary angiography in men over the age of 35 years, premenopausal women over the age of 35 years with coronary risk factors, and in postmenopausal women [1]. Since coronary disease and AS share common risk factors and pathogenic mechanisms it is important to evaluate for significant coronary artery disease so that bypass grafting can be performed with AVR if needed [1]. In general, patients with AS, whether mild, moderate or severe, have an increased risk of coronary heart disease events. In one study more than 90% of patients with severe AS developed coronary artery disease events over a 20 months period [4]. The decision for placement of a mechanical vs. a bio-prosthetic valve during AVR has been recently reviewed and should balance between the durability of the valve prosthesis and the bleeding risk of anticoagulation [63,64]. The increased risk from anticoagulation needed for mechanical valves and the improved durability of bio-prosthetic valves with increasing age would argue for the increased use of the later valve type in older adults. Nevertheless, almost 40% of aortic valves placed in individuals older than 90 years are metallic [65]. 6.2. Percutaneous AVR While AVR is currently the only effective therapy for symptomatic severe AS, around one third of patients for whom AVR is indicated do not undergo the procedure [66]. This is mostly due to advancing age and

comorbid conditions that place these patients at high surgical risk. The development of percutaneous AVR is opening new possibilities for the treatment of AS patients using minimally invasive procedures without the need for open heart surgery [67]. This exciting novel therapy is especially attractive in older adults who are not candidates for surgical AVR [68,69]. Since the introduction of this technique multiple valves have been developed that include valves mounted on self-expanding frames and others mounted on balloon-expandable stents [67,70]. These valves can be implanted in the stenotic aortic valve either via a retrograde approach from a peripheral artery (most commonly the femoral artery) using a large diameter sheath, or less often via a transapical approach where the valve is advanced through a sheath directly placed in the apex of left ventricle [71]. This more invasive approach is usually reserved for patients with peripheral vascular disease that preclude the use of the retrograde approach. Studies performed so far on percutaneous AVR have demonstrated the feasibility, safety, practicality, and efficacy of this approach [67,71]. Ongoing multi-center prospective randomized studies will compare this technique to medical therapy in patients who are not candidates for surgical intervention, and to surgical AVR in patients at high surgical risk. However there is paucity of data on the long-term durability of

Fig. 8. Paravalvular aortic prosthetic regurgitation. (A) Two-dimensional transesophageal echocardiogram. In this patient with a metallic prosthesis, color Doppler signals fill the whole extent of proximal left ventricular outflow tract in diastole consistent with severe aortic regurgitation (AR). It is difficult to assess the site of AR but it appears primarily valvular, not paravalvular. (B) Live/real time three-dimensional transesophageal echocardiogram. Paravalvular (P) regurgitation is located at the 7 o'clock position. Two jets of valvular (V) regurgitation are also visualized within the confines of the prosthesis. AO = aorta; LA = left atrium; MV = mitral valve. (Reproduced with permission from Singh P. et al. Live/Real Time Three-Dimensional Transesophageal Echocardiographic Evaluation of Mitral and Aortic Valve Prosthetic Paravalvular Regurgitation. Echocardiography 2009;26:980–7).

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prosthetic valves placed percutaneously and on the role of this procedure in patients who are candidates for surgical AVR [72]. Proper selection of candidates for this procedure is vital. In addition to the usual criteria for determining the need of and benefit from AVR, there are additional concerns that are particular for percutaneous AVR. The presence of severe peripheral vascular disease, severe angulation of the aorta, and/or significant atherosclerotic disease in the aorta may limit the use of the retrograde approach to the valve [73]. Proper sizing of the valve is important for decreasing complications. Valves are slightly oversized as compared to the aortic annulus in order to decrease paravalvular regurgitation and to securely anchor the valve which will decrease valve dislodgement and embolization [67]. Nevertheless, significant oversizing may result in the catastrophic rupture of the aortic annulus or obstruction of the coronary artery ostia [74]. Currently, 2DTTE is most often used for the pre-procedure sizing of the aortic annulus but this may underestimate the true annular diameter [73]. Imaging modalities that can visualize the aortic root in 3D such as computed tomography and 3DTTE/3DTEE are more accurate for this purpose and may potentially decrease the complication rate seen with this procedure. With 3DTTE, the entire aortic root can be captured in the 3D pyramidal dataset and then sectioned in any direction which provides the needed confidence in determining the proper prosthesis size for the patient. Percutaneous AVR is performed without the luxury of direct visualization and therefore relies heavily on multimodality imaging for real-time guidance during the procedure [73,75]. This is currently done with fluoroscopic and/or 2DTEE, but these modalities are limited by their 2D perspective. Positioning the prosthesis in relation to the native valve and the aortic annulus is inherently a 3D procedure. More precise localization of the prosthetic valve for final deployment and release can be done using 3D echocardiography. While transesophageal echocardiography is routinely used during open heart surgeries, transthoracic echocardiography is more versatile and has a long history of guiding percutaneous procedures in the catheterization laboratory [76]. Whether 3DTTE or 3DTEE will ultimately be used in guiding percutaneous AVR is not clear, both are more suited than 2D echocardiography for interrogating the prosthetic valve in the immediate post-deployment period for the assessment of paravalvular aortic regurgitation and deciding whether further balloon dilatations should be performed before the patient leaves the intervention suite (Fig. 8) [77,78]. 7. Conclusion AS is the most common valvular pathology in older adults. The clinical presentation of AS in this age group is complicated by the difficulty in symptom recognition due to decreased activity and the abundance of multiple comorbidities. Nevertheless, the development of symptoms from AS is a harbinger of quick deterioration and should signal the need for prompt intervention. Echocardiography can reliably and non-invasively assess the presence and severity of AS and select patients in need for intervention. The initial evaluation relies on Doppler interrogation with 2DTTE of the velocity across the valve which translates into an estimation of aortic valve orifice area. The aortic valve area can be directly measured using live/real-time 3DTTE avoiding the errors encountered with Doppler derived pressure gradients. Although medical therapy can be considered for the alleviation of symptoms in patients who are not candidates for surgical intervention, no medical therapy has been shown to prolong life making AVR the only approved therapy shown to improve the prognosis of patients with symptomatic AS. The recent development of the less invasive percutaneous AVR promises to revolutionize the treatment of AS in older adults. This procedure is currently being studied for the treatment of AS patients who are not candidates for the more conventional surgical intervention and success in this population may hasten the performance of clinical studies to assess the

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