STATE-OF-THE-ART PAPER
Management of Asymptomatic Severe Aortic Stenosis
Jacob P. Dal-Bianco, MD*,
Bjoy K. Khandheria, MBBS, FACC, FASE, FESC ,
Farouk Mookadam, MD, FRCP, MSc,
Federico Gentile, MD and
Partho P. Sengupta, MBBS, MD, DM,*
* Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, Arizona
Manuscript received May 5, 2008;
revised manuscript received June 30, 2008,
accepted July 1, 2008.
* Reprint requests and correspondence: Dr. Partho P. Sengupta, Division of Cardiovascular Diseases, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, Arizona 85259 (Email: sengupta.partho{at}mayo.edu).
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Abstract
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Patients with symptomatic severe aortic stenosis (AS) benefit from aortic valve replacement (AVR). Management of severe AS in the absence of symptoms is, however, controversial and often challenging. Unselected premature AVR carries the risks of cardiac surgery; delayed AVR due to unrecognized symptoms can result in a dismal outcome. Echocardiography is the standard tool to evaluate and follow patients with AS. Nevertheless, most of the current echocardiographic parameters have limitations in predicting symptom onset and clinical outcome. The same applies to clinical parameters, exercise stress testing, and other imaging modalities used in AS evaluation and serial follow-up. Predictors of outcome could, however, help to identify asymptomatic patients who would benefit from expedited AVR with the goal to reduce mortality. This review will discuss the most relevant clinical studies and guidelines on management of asymptomatic severe AS, with an emphasis on providing concise information for identifying patients at high risk.
Key Words: aortic stenosis • asymptomatic • management • outcome • predictor • severe
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Abbreviations and Acronyms
| | ACC/AHA = American College of Cardiology/American Heart Association | | AS = aortic stenosis | | AVA = aortic valve area | | AVR = aortic valve replacement | | BAV = bicuspid aortic valve | | BNP = brain natriuretic peptide | | CI = confidence interval | | CR = contractile reserve | | ESC = European Society of Cardiology | | HR = hazard ratio | | LV = left ventricle/ventricular | | LVEF = left ventricular ejection fraction | | OR = odds ratio | | RR = relative risk |
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Every fourth patient over age 65 years has evidence of aortic sclerosis (1), and more than 4% of the North American population age 75 years and older have aortic stenosis (AS) (2). Approximately 1 in 6 aortic sclerosis patients advances to AS (3), and in already established mild-to-moderate AS, one-half of those affected progress to hemodynamically severe AS (4).
Survival of patients with symptomatic AS is dismal (5–8), and the treatment of choice is aortic valve replacement (AVR) (9). Current AVR indication and timing is largely based on the development of angina, dyspnea, or syncope (10), and successful AVR results in good long-term prognosis (11,12). However, management of severe AS in the absence of symptoms is challenging. Whereas lack of symptom recognition portends a high risk of death (13), unselected, premature AVR is associated with the risks of cardiac surgery and valve prosthesis complications. At least every third—with estimates up to every second—patient with severe AS is asymptomatic (5,14,15). This makes reliable risk estimation and appropriate AVR indication and timing in patients with asymptomatic severe AS a common and important clinical challenge.
For this review we searched the MEDLINE database with PubMed. Our queries included the Medical Subject Heading term "Aortic Valve Stenosis" in various combinations with "asymptomatic," "outcome," "predictor," "survival," and "mortality." Search results were restricted to original articles, reviews, and editorials in the English language. Additionally we retrieved articles referenced by published guidelines and comprehensive reviews.
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Calcific Aortic Valve Disease: From Aortic Sclerosis to AS
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Calcific aortic valve disease is the leading AS etiology in industrialized countries (2,16–18) and shares the atherosclerosis risk factors age, gender, hypertension, smoking, serum low-density lipoprotein, and lipoprotein (a) levels (1). Aortic valve calcification is a complex pathological process that starts at the base of the aortic cusp (10), primarily in response to endothelial damage caused by blood flow shear stress, and is followed by inflammatory cell infiltration, lipid and calcium deposition, and activation of osteoblast-like cells (19–25). Disease progression might be potentially modifiable by anti-inflammatory and lipid-lowering therapy (HMG-CoA reductase inhibitors) (26–30); however, if progressive, calcification usually spreads to the leaflet tips causing thickening, stiffening, and restricted movement of the aortic valve leaflets. Calcific aortic valve disease can be nonobstructive (= aortic sclerosis) or obstructive (= AS). Aortic stenosis can be graded, on the basis of the severity of obstruction, as mild, moderate, or severe (Table 1).
The average time interval from development of aortic sclerosis to moderate and severe AS is 6 and 8 years, respectively (3). This gives the left ventricle (LV) time to remodel for counteracting the increase in afterload (31,32). Reduction in LV longitudinal shortening due to subendocardial dysfunction (33) is accompanied with adaptive concentric wall hypertrophy (34) and exaggerated LV torsional mechanics (35) to keep LV systolic wall stress and left ventricular ejection fraction (LVEF) initially within the normal range. Once moderate AS is present the average rate of aortic jet velocity progression by cardiac ultrasound is 0.3 m/s/year, with a concomitant increase in the mean transvalvular pressure gradient of 7 mm Hg/year and a parallel reduction in aortic valve area (AVA) of 0.1 cm2/year (11,36–38). Hemodynamic progression and calcification are accelerated in patients with congenital aortic valve disease (39). Patients with bicuspid aortic valve disease (BAV) present for AVR earlier (fourth decade) in comparison with patients with tricuspid AS (sixth decade) (18).
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Natural History of Asymptomatic AS
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Ross and Braunwald (40) published a comprehensive report on the natural history of AS, summarizing prospective and retrospective (post-mortem) studies and their experience. Patients with AS who developed angina and syncope survived 3 years, patients with dyspnea 2 years, and patients with heart failure survived 1.5 to 2 years, respectively. This landmark survival analysis from 1968 included symptomatic patients with heterogeneous AS etiologies (e.g., bicuspid AS; rheumatic AS [41]), which might limit applicability in today's most common AS etiology—tricuspid calcific AS.
Several retrospective (14,42) and prospective studies (11,43) have subsequently specifically evaluated the prognosis and management of patients with asymptomatic severe AS. It is important to note that these studies differed in design (e.g., patient age, exclusion criteria, mean transvalvular gradient). For example, Otto et al. (43) included patients with less than severe AS and bicuspid AS (28% of the study population). Secondly, AVR was considered as a clinical end point in each of these studies (Table 2). This makes survival data less conclusive, because AVR is a "soft" clinical end point compared with cardiac death. Moreover, referral for AVR might have been confounded by the primary physician's treatment bias ("pre-emptive" AVR vs. true symptom development) or AVR performed concomitantly with coronary artery bypass grafting. Thirdly, coronary artery disease was not an exclusion criterion and potentially confounded cardiac death. Despite these limitations, it is worthwhile noting that approximately one-third of asymptomatic AS patients become symptomatic within 2 years (42). Within 4 to 5 years, two-thirds of patients have either an AVR due to symptom development or cardiac death (11,14,43). Survival in asymptomatic and unoperated patients is 99%, 98%, and 93% at 1, 2, and 5 years, respectively. Survival in these patients is actually similar to an age- and gender-matched healthy population; however, the prognosis worsens significantly as soon as symptoms develop (14). Overall survival of patients with asymptomatic severe AS including those who have AVR is 93 ± 2%, 91 ± 3%, and 87 ± 3% at 1, 2, and 5 years, respectively, which again does not differ statistically from an age- and gender-matched population (11). Early estimates of sudden death without preceding symptoms were approximately 3% to 5%/year (40). More recent evidence supports the concept that sudden death in truly asymptomatic AS patients is <1%/year (5,7,11,42,43). This conservative number, however, might be generated by heightened clinical vigilance, where patients are followed meticulously with serial echocardiography, and might not be representative of the ambient annual risk of sudden death in this group of patients.
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Diagnosis of AS and Grading of Severity
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On the basis of 2-dimensional echocardiography and Doppler measurements, AS can be graded as mild, moderate, and severe (Table 1) (10,44). In general, aortic jet velocity is the most reproducible measurement (45,46), because even small errors in LV outflow tract diameter and ultrasound beam alignment with respect to the aortic jet profoundly influence the calculated AVA and mean and peak transvalvular pressure gradient. Significant aortic regurgitation has limited impact on Doppler-calculated AVA, whereas a chaotic subvalvular velocity profile due to subvalvular obstruction (e.g., septal hypertrophy or subaortic membrane) results in erroneous AVA quantification (47). Furthermore, it needs to be emphasized that serial echocardiographic evaluation should be performed in a state of comparable hemodynamic range (46,48), because interexamination blood pressure differences, especially acute hypertension, can mask AS severity by influencing transvalvular pressure gradient and jet velocity (49).
Because noninvasive transvalvular gradients show excellent correlation with invasive transvalvular gradients, cardiac catheterization is rarely used to diagnose AS (50). Invasive hemodynamics, however, might be of value in patients in need of coronary angiogram whose Doppler-derived transvalvular gradients are disproportionate to physical exam findings or patient history. An example is a patient with a small ascending aorta diameter (<3 cm) where pronounced pressure recovery might lead to significant Doppler overestimation of transvalvular gradient and therefore AS severity (51).
More recently, 3-dimensional echocardiography (52–55), cardiac computerized tomography (56,57), and cardiac magnetic resonance imaging (58–60) have been proposed as additional techniques to quantify AVA and AS severity. Because these imaging modalities measure the anatomic and not the functional effective AVA, AS severity is more likely to be underestimated. A new and exciting magnetic resonance imaging technique, overcoming the limitations of anatomic quantification of the AVA, is velocity-encoded phase contrast imaging (Fig. 1) (60–62). This method allows AVA quantification with the continuity equation mimicking echocardiographic Doppler quantification and should be helpful in patients with poor echocardiographic windows, obesity, lung disease, or heavily calcified aortic valves. Contrary to current "crude" conventional measures such as LVEF, tissue Doppler imaging and speckle track imaging (Fig. 2) are superior in detecting subtle changes in myocardial function. Studies have shown reduced longitudinal systolic and early diastolic mitral annular velocities in patients with AS (63–65) and evidence of early LV systolic dysfunction if peak systolic mitral annular velocity increase after treadmill exercise is blunted (66). Longitudinal strain and strain rates are also reduced but show significant improvements after AVR, even before global LV function improves (67). Left ventricular torsion is a measure of the "wringing" motion of the heart and plays a critical role in efficient blood expulsion and filling. Systolic LV torsion is preserved or exaggerated in AS (35,68) and likely compensates for depressed intramyocardial circumferential strain (69) and decreased subendocardial contractile function (70) (Fig. 3). Diastolic untwisting is delayed, resulting in elevated LV end-diastolic filling pressures (35,68). Left ventricular torsion normalizes (69) and subendocardial contractile function significantly recovers within 3 month after AVR—even before LV remodeling is obvious (70). Early detection of myocardial dysfunction by tissue Doppler and speckle track imaging (Fig. 2) might be therefore potentially useful in optimizing the timing of AVR before the onset of global LV dysfunction and symptoms in patients with severe AS (33). However, this requires future investigation.
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Figure 1 Velocity-Encoded Phase Contrast Magnetic Resonance Imaging in Aortic Stenosis
Sampling planes in the left ventricular outflow tract and after the aortic valve allow measurement of quantitative flow by velocity time integration (gray area under the curve). Functional aortic valve area is then calculated by continuity equation. Adapted, with permission, from Caruthers et al. (62).
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Figure 2 Longitudinal Left Ventricular Mechanics in Asymptomatic Severe Aortic Stenosis
Continuous wave Doppler signal across the stenotic aortic valve (A) shows a peak and mean gradient of 80 and 44 mm Hg, respectively. Pulsed wave tissue Doppler from the septal corner of the mitral valve annulus (B) shows a reduced peak early diastolic longitudinal relaxation velocity (5 cm/s). Longitudinal strain obtained by speckle tracking (2D strain, GE Healthcare, Milwaukee, Wisconsin) shows attenuated peak longitudinal strain (C and D) from apical (green curve), mid (yellow curve), and basal (blue curve) of the lateral wall of the left ventricle (peak strain values <10%). Dotted white line (D) also shows a reduced global longitudinal strain averaged from the septum and lateral wall of the left ventricle (global strain = 12%). Aa = peak late diastolic annular velocity; Ea = peak early diastolic annular velocity; Sa = peak systolic velocity during ejection.
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Figure 3 Exaggerated LV Twist Mechanics in Aortic Stenosis
Peak counterclockwise rotation from apex (A) and clockwise rotation from base (B) are obtained by speckle track imaging (2D strain, GE Healthcare) of LV short-axis views of the patient shown in Figure 2. The difference of the 2 rotational values provides the peak net twist angle. This example illustrates presence of exaggerated LV rotation, particularly near the LV base with relatively high net LV twist angle value. AVC = aortic valve closure; LV = left ventricle.
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Risk Estimation in Asymptomatic Severe AS
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A major clinical challenge is to manage asymptomatic patients with severe AS when the lack of clinical symptoms and echocardiographic findings do not support AVR per guidelines. The physician has to weigh the individual patient risks for AVR surgery versus watchful waiting with potential risk of sudden cardiac death or AVR at a more advanced age (71). Identifying at-risk patients would allow optimized AVR timing and "controlled" anticipation of AVR, while meeting the goals of avoiding unnecessary surgery and improving long-term mortality. The following section will elucidate the current concepts of risk estimation in patients with asymptomatic severe AS. Table 3
summarizes the predictors for symptoms, outcome, and operative mortality.
Predictors of Symptom Development.
Electrocardiography
In a multivariate analysis, LV hypertrophy defined by Romhilt and Estes criteria (72) was found to be an independent predictor for the development of symptoms in asymptomatic severe AS patients (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.02 to 1.89; p = 0.04) (14). The sensitivity for detecting LV hypertrophy by electrocardiogram, however, might be as low as 40%.
Echocardiography
Patients with asymptomatic severe AS and a peak aortic jet velocity  4.5 m/s are more likely to develop symptoms compared with patients with a peak aortic jet velocity <4.5 m/s (relative risk [RR]: 1.34; 95% CI: 1.04 to 1.72; p = 0.03) (14). The same investigators showed that: 1) each 0.2-cm2 decrease in AVA translates into an RR of 1.26 likelihood of developing symptoms (95% CI: 1.08 to 1.47; p = 0.004); and 2) AVA is an independent predictor for the development of symptoms (HR: 0.33 for a 1-cm2 increase; 95% CI: 0.15 to 0.71; p = 0.005) (14). Although these data allow risk estimation of symptom development, there are no echocardiographic parameters to estimate the timing of symptom onset.
Exercise stress testing
Das et al. (73) prospectively evaluated 125 patients with asymptomatic mild (n = 11), moderate (n = 62), and severe AS (n = 52) to assess the accuracy of treadmill exercise testing in predicting symptom onset within 12 months. Twenty-one patients with a positive stress test met the combined end points of spontaneous exertional symptoms or cardiac death. Symptom-free survival at 12 months was 49% versus 89% for patients with a symptom limited exercise test compared with those without a symptom limited exercise test. In a multivariate analysis only the development of symptoms during stress testing was found to predict symptom onset within 12 months (odds ratio [OR]: 7.7; 95% CI: 2.79 to 21.39; p < 0.001). Analysis of the patient subgroup with severe AS (n = 52) showed a positive and negative predictive accuracy of 65% and 73%, respectively, for subsequent symptom development after a symptom limited exercise test. Interestingly, however, the type of exercise-induced symptom seems to be important: compared with breathlessness or chest tightness, exertional dizziness seems to be a relatively reliable marker for subsequent symptom development (54% vs. 50% vs. 83%). Breathlessness and chest tightness seem to be nonspecific symptoms secondary to physical fitness and exercise tolerance rather than AS. Accordingly, stress testing has been found to be of higher diagnostic value in patients  70 years old in specific activity scale class I (= patient can complete any activity requiring 7 metabolic equivalents [74]) (Table 4).
Cardiac biomarkers
Bergler-Klein et al. (75) reported that asymptomatic severe AS patients with brain natriuretic peptide (BNP) or N-terminal BNP concentrations of <130 pg/ml and 80 pmol/l, respectively, had a 9-month symptom-free survival of close to 90%. Patients with higher natriuretic peptide concentrations frequently required surgery (symptom-free survival <50%). Kaplan-Meier analysis in patients with BNP levels <130 pg/ml (n = 25) versus 130 pg/ml (n = 18) showed symptom-free survival of 100% versus 94 ± 5% at 3 months, 90 ± 7% versus 64 ± 12% at 6 months, 90 ± 7% versus 45 ± 14% at 9 months, and 66 ± 16% versus 34 ± 14% at 12 months (p < 0.05). Only N-terminal BNP independently predicted symptom-free survival. Asymptomatic status was defined as freedom of shortness of breath, angina, dizziness, and syncope with exertion and symptom status assessed blinded to the results of BNP and N-terminal BNP. Serial measurements of these markers might therefore add incremental information to help to identify optimal AVR timing (15).
Predictors of Clinical Outcome.
Clinical parameters
Age: event-free survival (AVR, cardiac death, noncardiac death) for patients with asymptomatic severe AS and age 50 years or younger has been found to be significantly higher (85 ± 6% vs. 59 ± 6% at 1 year, 69 ± 8% vs. 49 ± 6% at 2 years, and 59 ± 9% vs. 21 ± 5% at 4 years [p < 0.001]) (11). Baseline functional status score: in a multivariate regression analysis model, Otto et al. (43) showed that the baseline Functional Status Questionnaire (76) score was predictive of clinical outcome (p = 0.002) (43). Patients who remained asymptomatic during follow-up had a significantly higher baseline and final Functional Status Questionnaire score (96 ± 7%; 95 ± 7%) compared with those meeting a clinical end point (92 ± 2%; 85 ± 16%) (patient population included asymptomatic patients with less than severe AS and BAV disease) (43).
Echocardiography
Baseline aortic jet velocity, the rate of change over time in aortic jet velocity, and baseline AVA have been found to predict clinical outcome (AVR, cardiac death) (43).
Patients with a baseline aortic jet velocity below 3.0 m/s and between 3.0 and 4.0 m/s have a 2-year event-free survival (without AVR) of 84 ± 16% and 66 ± 13%, respectively. Patients with an aortic jet velocity >4.0 m/s had a 21 ± 18% likelihood of being alive at 2 years (patient population included asymptomatic patients with less than severe AS and BAV disease) (43). Compared with patients with asymptomatic severe AS and a peak aortic jet velocity <4.5 m/s, patients with asymptomatic severe AS and a peak aortic jet velocity of 4.5 m/s have an increased RR of a cardiac event (AVR; cardiac death; RR: 1.48; 95% CI: 1.20 to 1.81; p = 0.0002) (14).
Aortic-jet velocity progression is significantly higher in patients with asymptomatic severe AS and cardiac events (AVR; cardiac death; noncardiac death) compared with those without a cardiac event (0.45 ± 0.38 m/s/year vs. 0.14 ± 0.18 m/s/year, p < 0.001) (11).
Patients with asymptomatic severe AS and a reduced LVEF (<50%) have been found to have a higher RR of sustaining cardiac events (AVR; cardiac death second to AS; RR: 5.6; 95% CI: 1.46 to 21.3; p = 0.01) (42).
With regard to AVA, the RR of a cardiac event (AVR; cardiac death) has been found to increase per 0.2-cm2 decrease in AVA (RR: 1.20; 95% CI: 1.06 to 1.36; p = 0.006) (14).
Event-free survival (AVR; cardiac death; noncardiac death) for patients without or with mild calcification versus patients with moderate or severe calcification has been found to be 92 ± 5% versus 60 ± 6% at 1 year, 84 ± 8% versus 47 ± 6% at 2 years, and 75 ± 9% versus 20 ± 5% at 4 years (p < 0.001) (11).
Stroke-work loss, the ratio of the mean transvalvular pressure gradient and LV pressure, has also been proposed to predict cardiac events (AVR; cardiac death) in asymptomatic AS patients. A stroke-work loss >26% results in a probability of cardiac death or AVR of >30% in the following 3 months (77).
Exercise stress testing
Several studies have evaluated the value of exercise stress testing in predicting clinical outcome in asymptomatic severe AS (Table 5). Amato et al. (78) prospectively followed 66 patients with asymptomatic severe AS (AVA 1.0 cm2) for a mean follow-up of 15 ± 12 months. Patients with a positive stress test (n = 44) had a 2-year event-free survival of only 19% compared with 85% if symptom-free during exercise. It is important to point out that event-free survival was defined as absence of symptoms in daily life and/or sudden death. Thirty-five patients met the combined end points (symptom development n = 31; sudden cardiac death n = 4). Positive and negative predictive values for a positive stress test and subsequent end point development were 0.79 and 0.86, respectively. The estimated risk to reach the combined end point for patients with a positive stress test was 7.6 times higher than in patients with a negative stress test. Every patient who died during the study follow-up had an AVA <0.7 cm2. It seems reasonable to conclude that patients with a negative exercise test seem to have a good outcome and might not require AVR.
Exercise stress echocardiography
Lancellotti et al. (79) recently evaluated the incremental prognostic information of quantitative exercise Doppler echocardiography over clinical, resting echocardiographic, and stress electrocardiographic parameters in patients with asymptomatic severe AS. Resting to peak exercise increase of mean aortic transvalvular gradient of >18 mm Hg and an AVA <0.75 cm2 were found to independently predict cardiac events (angina, dyspnea, and syncope; hospital admission for heart failure; cardiac death; AVR).
Electron-beam computed tomography
Like Rosenhek et al., Messika-Zeitoun et al. (80) observed that aortic valve calcification predicted event-free survival defined as survival without dyspnea, angina, syncope, heart failure, or need for surgery. Adjusted RR was 1.06 (95% CI: 1.02 to 1.10) per 100-Agatston units increment (p < 0.001). Event-free survival at 5 years was 92 ± 4% versus 40 ± 18% comparing patients with calcification below and above 500 Agatston units, respectively (p = 0.0002). Aortic valve calcification also independently predicted event-free survival in patients with no or minimal symptoms (RR: 1.09/100 Agatston units; 95% CI: 1.05 to 1.15; p < 0.0001). Data further supporting the predictive value of calcification were recently reported by Feuchtner et al. (81). Electron-beam computed tomography offers the advantage of objective calcification quantification (in Agatston units) as compared with the subjective grading by echocardiography.
When interpreting predictors of clinical outcome it is important to remember that survival outcomes included AVR as a clinical event, creating the conundrum that AVR is predictive of AVR.
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Management of Patients With Asymptomatic Severe AS
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Onset of symptoms in a patient with AS who has been previously asymptomatic, if unnoticed even only for a few months, carries a bleak prognosis (6,13). Therefore, every patient with asymptomatic severe AS should be educated and advised to self-report onset of new symptoms (10). Some patients might subconsciously adapt and reduce their daily activities, and in these spuriously "asymptomatic" AS patients exercise stress testing has been shown to uncover symptoms in more than one-third of patients (73). There are, however, caveats in exercise stress testing symptom interpretation: 1) concurrent or unsuspected coronary artery disease potentially mimics AS symptoms (angina) (10); and 2) physical fitness influences reliable AS symptom interpretation. Close clinical follow-up in any patient with asymptomatic severe AS is recommended (6 to 12 months), and if there is no echocardiographic evidence of rapid progression in 2 independent evaluations performed 6 months apart, patients should continue to follow up clinically with an annual echocardiographic examination. Expedited patient re-evaluation is warranted if there is a change in clinical status (10,82). Hypertension is common in patients with severe AS (approximately 30%) and should be aggressively treated in patients with asymptomatic AS (83). There is limited information regarding the role of statin therapy in delaying progression of asymptomatic AS (26–30). Two large, multicenter, double blinded, randomized, placebo-controlled trials—1) SEAS (Simvastatin and Ezetimibe in AS) and 2) ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effect of Rosuvastatin)—will hopefully clarify the role of statins in calcific AS.
Figure 4
provides a suggested stepwise approach in managing patients with asymptomatic severe AS on the basis of current American (American College of Cardiology/American Heart Association [ACC/AHA]) (10) and European (European Society of Cardiology) (84) AVR guidelines. It is worthwhile pointing out that even the recommendations with current best evidence are mainly based on expert consensus and/or small studies, retrospective studies, and registries.
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Figure 4 Stepwise Evaluation of Patients With Severe AS on the Basis of ACC/AHA and ESC Recommendations
Levels of evidence are provided in parentheses (American College of Cardiology/American Heart Association [ACC/AHA]; European Society of Cardiology [ESC]) (10,84). AS = aortic stenosis; AVA = aortic valve area; AVR = aortic valve replacement; BNP = brain natriuretic peptide; BP = blood pressure; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CR = contractile reserve; EBCT = electron beam computed tomography; LV = left ventricle; LVEF = left ventricular ejection fraction.
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Benefits, Risks, and Alternatives to AVR
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Pre-emptive AVR in asymptomatic severe AS could theoretically reduce progressive myocardial dysfunction, which has been shown to be a predictor of heart failure and death after AVR (85). Iung et al. (86) speculated that nearly one-third of patients with symptomatic severe, single-valve heart disease who could benefit from AVR do not undergo surgical repair. Timely surgery at an asymptomatic stage could therefore potentially reduce the likelihood of being deemed a nonsurgical candidate when symptomatic.
Potential benefits of AVR in asymptomatic severe AS have to be weighed against short-term perioperative risks and the long-term risks of thromboembolism, anticoagulation-related bleeding, and infective endocarditis. Although no intervention, but observation only, has low risks (sudden cardiac death <1%/year), average surgical mortality for isolated AVR is approximately 3% to 4% (86) and 1% to 2% in high-volume and experienced medical centers (10). Surgical mortality, however, increases progressively with age and is up to 9% in octogenarians (87–92). Additional factors can further increase the risk of operative mortality in asymptomatic severe AS (e.g., emergent surgery, LV dysfunction, pulmonary hypertension, coexisting coronary artery disease, and previous bypass or valve surgery) (84). The ACC/AHA guidelines make the choice of AVR prosthesis type dependent on concurrent mitral or tricuspid mechanical valve, anticoagulation contraindications, thrombosis risk, and patient preferences (10). The incidence of thromboembolism and bleeding related to anticoagulation in the setting of a mechanical aortic valve prosthesis is 1.1 and 4.6/100 patient-years, respectively (93), with the latter increasing significantly if patients are 75 years of age (94). The incidence of infective endocarditis has been reported to be 0.27%/patient-year (95). These specific incidence rates, however, vary depending on the type of mechanical aortic valve prosthesis (96). Bioprosthetic aortic valves have the main risk of structural valve degeneration and therefore reduced valve life. Interestingly, however, a recent meta-analysis did not find any differences in mortality in patients with mechanical or bioprosthetic aortic valves (97). A bioprosthetic aortic valve is currently a reasonable choice in adult patients (approximately 65 years of age) who have contraindications to anticoagulation or who decline or do not require anticoagulation (10).
Aortic balloon valvotomy as an alternative to AVR is associated with significant procedural risk (98) and restenosis (99) and is currently only recommended for the unstable, severely comorbid adult patient with severe AS (10). In contrast, percutaneous AVR has attracted an unprecedented interest (100). One can speculate that the role of percutaneous AVR might be expanded to patients with asymptomatic severe AS who are "assumed" to be high-risk candidates for surgical AVR; however, this will need to be addressed in future studies.
Selected Clinical Scenarios.
The asymptomatic patient with less than severe AS
Management of the asymptomatic patient with less than severe AS is challenging, and evidence to support "pre-emptive" AVR is limited. Current guidelines support AVR during coronary artery bypass grafting or ascending aorta surgery in: 1) patients with asymptomatic moderate AS (Class IIa-B); and 2) patients with mild AS and potential rapid AS progression (Class IIb-C) (10). Serial echocardiographic examinations might identify such "rapid progressors," a high-risk group of patients with moderately or severely calcified aortic valves in whom aortic jet velocity increases by 0.3 m/s within 1 year (2-year risk of AVR or death of 79%) (11).
The comorbid patient
Patients with asymptomatic and moderate-to-severe AS and progressive medical comorbidities (e.g., advanced age and impaired renal function) might be deemed inoperable once AVR is indicated (86). Pre-emptive AVR might be justified in some of these patients even at an asymptomatic stage. However, management strategies should be based on thorough risk estimation in regard to symptom development and AS progression ("rapid progressors"), medical center experience and surgery volume, and potential post-AVR benefit (e.g., reversibility/stabilization of renal function).
The patient in need of noncardiac surgery
Patients with asymptomatic severe AS who require emergent noncardiac surgery should proceed without AVR evaluation; in elective noncardiac surgery AVR management is dependent on coronary artery status (101). Depending on the type of noncardiac surgery and need for anticoagulation, AVR might be performed pre-emptively or simultaneously.
BAV disease
BAV disease is a disease of the aortic valve and ascending aorta (102) and frequently progresses to AS (18,103). Ascending aortic dilation is independent of AS severity (102) and affects up to 4 of 10 BAV patients over time (104). The most severe risk of aortic dilation, aortic dissection, has been reported to be 9 times higher in BAV compared with patients with tricuspid aortic valves (105). Evidence is scarce, but it seems reasonable to manage BAV patients similar to their tricuspid counterparts with the following additional criteria for follow-up of ascending aorta dilation. Aortic valve replacement should be considered if indicated by ACC/AHA (10) and European Society of Cardiology (84) guidelines with the addition of aortic root repair or ascending aorta replacement if more than 4.5 cm in diameter. Conversely, the aortic valve should be replaced in an asymptomatic patient with moderate or severe AS if aortic root repair or ascending aorta replacement is indicated due to ascending aorta diameter (>5.0 cm) or diameter increase by 0.5 cm/year or more (cut-off values should be adjusted depending on body stature) (10).
Low-gradient/low-flow AS
Patients with severe AS might have low-flow/low-gradient (<40 mm Hg) AS in the setting of reduced LVEF or preserved LVEF. Patients with severe AS and reduced LVEF are rarely asymptomatic, and therefore most of the available management data are derived from symptomatic patients (106–108). In patients with reduced LVEF it is important to determine whether the compromised LV function is attributable to a primary cardiomyopathy (e.g., scarred, fibrosed myocardium), ischemic LV dysfunction, or excessive afterload (= true, fixed AS), because the latter group of patients are most likely to benefit from AVR. Low-dose dobutamine stress hemodynamic echocardiography (20 µg/kg/min) identifies these patients by demonstrating contractile reserve (CR) (defined as a 20% stroke volume increase from baseline on the basis of LV outflow Doppler measurements [109]) and transvalvular gradient increase (confirming severe AS). Monin et al. (106) reported that presence of LV contractile reserve is predictive for long-term survival (HR: 0.40; 95% CI: 0.23 to 0.69; p = 0.001). Absence of contractile reserve (OR: 10.9; 95% CI: 2.6 to 43.4; p = 0.001) and a baseline mean transaortic gradient 20 mm Hg (OR: 4.7; 95% CI: 1.1 to 21.0; p = 0.04) predicted perioperative mortality. Evidence for contractile reserve resulted in reduced pre-operative mortality (CR+ vs. CR–: 5% vs. 32%) (106). Recovery of LVEF and post-operative 2-year survival in the absence of baseline contractile reserve, however, resembles that of patients with contractile reserve once patients survive 30 days after surgery (107). Therefore, AVR should not be contraindicated on the basis of documentation of exhausted contractile reserve alone. Bergler-Klein et al. (108) evaluated the prognostic value of BNP in 69 patients with low-flow, low-gradient AS, 7 (10%) of whom were New York Heart Association functional class I. One year after AVR, survival was markedly lower in patients with BNP 550 pg/ml (53 ± 13% vs. 92 ± 7%). Thus, BNP 550 pg/ml emerged as a significant predictor of outcome (p < 0.001). One has to note that patient numbers were low (n = 29), allowing only univariate analysis of BNP as a predictor of outcome. Nevertheless, these results could support AVR in patients with asymptomatic AS and reduced LVEF, even in the absence of contractile reserve if BNP levels are 550 pg/ml.
Low-flow severe AS patients have increased global LV afterload leading to pronounced LV concentric remodeling and a preserved LVEF, concealing impaired myocardial function (110). In this patient group, low stroke volumes reveal myocardial dysfunction and, due to reduced mean and maximal flow velocities and gradients (111), might lead to discrepantly low mean transvalvular gradients compared with AVA (112). The exact prevalence and management of asymptomatic patients with low-flow/low-gradient, severe AS and preserved LVEF is less clear. However, a recent retrospective study by Hachicha et al. (113) reported that AVR in these patients led to significantly improved survival and was preferable to medical treatment. The exact relevance of this finding for patients with asymptomatic severe AS who have low flow despite preserved LVEF remains to be established.
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Summary
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In asymptomatic patients with severe AS, AVR mortality and the yearly risks of prosthetic valve complications are greater than the yearly risks of watchful waiting. However, such patients must be closely monitored by regular clinical and echocardiographic follow-up and should be educated regarding symptom recognition and prompt self-reporting. Exercise stress testing should be considered if symptom status is unclear. Expedited AVR seems reasonable in patients with a higher risk profile (extensive aortic valve calcification, rapid aortic jet progression on serial echocardiograms, concomitant coronary artery disease, LV systolic dysfunction, elevated BNP levels, and in some cases before referral for major elective noncardiac surgery). Pre-emptive AVR might emerge as the treatment of choice in the future; however, this will be dependent on the (yet unproven) superiority of noninvasive myocardial function assessment and advances in prosthetic aortic valve design and percutaneous valve placement.
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References
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1. Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 1997;29:630-634.[Abstract]2. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study Lancet 2006;368:1005-1011.[CrossRef][Medline] 3. Cosmi JE, Kort S, Tunick PA, et al. The risk of the development of aortic stenosis in patients with "benign" aortic valve thickening Arch Intern Med 2002;162:2345-2347.[Abstract/Free Full Text] 4. Rosenhek R, Klaar U, Schemper M, et al. Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography. Eur Heart J 2004;25:199-205.[Abstract/Free Full Text] 5. Turina J, Hess O, Sepulcri F, Krayenbuehl HP. Spontaneous course of aortic valve disease Eur Heart J 1987;8:471-483.[Abstract/Free Full Text] 6. Horstkotte D, Loogen F. The natural history of aortic valve stenosis Eur Heart J 1988;9(Suppl E):57-64.[Abstract/Free Full Text] 7. Kelly TA, Rothbart RM, Cooper CM, Kaiser DL, Smucker ML, Gibson RS. Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis Am J Cardiol 1988;61:123-130.[CrossRef][Web of Science][Medline] 8. Iivanainen AM, Lindroos M, Tilvis R, Heikkila J, Kupari M. Natural history of aortic valve stenosis of varying severity in the elderly Am J Cardiol 1996;78:97-101.[CrossRef][Web of Science][Medline] 9. Lindblom D, Lindblom U, Qvist J, Lundstrom H. Long-term relative survival rates after heart valve replacement J Am Coll Cardiol 1990;15:566-573.[Abstract] 10. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons J Am Coll Cardiol 2006;48:e1-e148.[Free Full Text] 11. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis N Engl J Med 2000;343:611-617.[CrossRef][Web of Science][Medline] 12. Pai RG, Kapoor N, Bansal RC, Varadarajan P. Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement Ann Thorac Surg 2006;82:2116-2122.[Abstract/Free Full Text] 13. Chizner MA, Pearle DL, deLeon Jr AC. The natural history of aortic stenosis in adults Am Heart J 1980;99:419-424.[CrossRef][Web of Science][Medline] 14. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up Circulation 2005;111:3290-3295.[Abstract/Free Full Text] 15. Baumgartner H. Aortic stenosis: medical and surgical management Heart 2005;91:1483-1488.[Free Full Text] 16. Selzer A. Changing aspects of the natural history of valvular aortic stenosis N Engl J Med 1987;317:91-98.[Web of Science][Medline] 17. Dare AJ, Veinot JP, Edwards WD, Tazelaar HD, Schaff HV. New observations on the etiology of aortic valve disease: a surgical pathologic study of 236 cases from 1990 Hum Pathol 1993;24:1330-1338.[CrossRef][Web of Science][Medline] 18. Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation Circulation 2005;111:920-925.[Abstract/Free Full Text] 19. Agmon Y, Khandheria BK, Jamil Tajik A, et al. Inflammation, infection, and aortic valve sclerosis; Insights from the Olmsted County (Minnesota) population Atherosclerosis 2004;174:337-342.[Web of Science][Medline] 20. Olsson M, Dalsgaard CJ, Haegerstrand A, Rosenqvist M, Ryden L, Nilsson J. Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves J Am Coll Cardiol 1994;23:1162-1170.[Abstract] 21. Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O'Brien KD. Characterization of the early lesion of ‘degenerative’ valvular aortic stenosis. Histological and immunohistochemical studies. Circulation 1994;90:844-853.[Abstract/Free Full Text] 22. O'Brien KD, Reichenbach DD, Marcovina SM, Kuusisto J, Alpers CE, Otto CM. Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of ‘degenerative’ valvular aortic stenosis Arterioscler Thromb Vasc Biol 1996;16:523-532.[Abstract/Free Full Text] 23. Mohler III ER, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves Circulation 2001;103:1522-1528.[Abstract/Free Full Text] 24. Wallby L, Janerot-Sjoberg B, Steffensen T, Broqvist M. T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves Heart 2002;88:348-351.[Abstract/Free Full Text] 25. Rajamannan NM, Subramaniam M, Rickard D, et al. Human aortic valve calcification is associated with an osteoblast phenotype Circulation 2003;107:2181-2184.[Abstract/Free Full Text] 26. Bellamy MF, Pellikka PA, Klarich KW, Tajik AJ, Enriquez-Sarano M. Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community J Am Coll Cardiol 2002;40:1723-1730.[Abstract/Free Full Text] 27. Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis N Engl J Med 2005;352:2389-2397.[CrossRef][Web of Science][Medline] 28. Moura LM, Ramos SF, Zamorano JL, et al. Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis J Am Coll Cardiol 2007;49:554-561.[Abstract/Free Full Text] 29. Rosenhek R, Rader F, Loho N, et al. Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis Circulation 2004;110:1291-1295.[Abstract/Free Full Text] 30. Shavelle DM, Takasu J, Budoff MJ, Mao S, Zhao XQ, O'Brien KD. HMG CoA reductase inhibitor (statin) and aortic valve calcium Lancet 2002;359:1125-1126.[CrossRef][Web of Science][Medline] 31. Spann JF, Bove AA, Natarajan G, Kreulen T. Ventricular performance, pump function and compensatory mechanisms in patients with aortic stenosis Circulation 1980;62:576-582.[Free Full Text] 32. Sasayama S, Ross Jr. J, Franklin D, Bloor CM, Bishop S, Dilley RB. Adaptations of the left ventricle to chronic pressure overload Circ Res 1976;38:172-178.[Abstract/Free Full Text] 33. Poulsen SH, Sogaard P, Nielsen-Kudsk JE, Egeblad H. Recovery of left ventricular systolic longitudinal strain after valve replacement in aortic stenosis and relation to natriuretic peptides J Am Soc Echocardiogr 2007;20:877-884.[CrossRef][Web of Science][Medline] 34. Krayenbuehl HP, Hess OM, Ritter M, Monrad ES, Hoppeler H. Left ventricular systolic function in aortic stenosis Eur Heart J 1988;9(Suppl E):19-23.[Abstract/Free Full Text] 35. Stuber M, Scheidegger MB, Fischer SE, et al. Alterations in the local myocardial motion pattern in patients suffering from pressure overload due to aortic stenosis Circulation 1999;100:361-368.[Abstract/Free Full Text] 36. Otto CM, Pearlman AS, Gardner CL. Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography J Am Coll Cardiol 1989;13:545-550.[Abstract] 37. Roger VL, Tajik AJ, Bailey KR, Oh JK, Taylor CL, Seward JB. Progression of aortic stenosis in adults: new appraisal using Doppler echocardiography Am Heart J 1990;119:331-338.[Web of Science][Medline] 38. Brener SJ, Duffy CI, Thomas JD, Stewart WJ. Progression of aortic stenosis in 394 patients: relation to changes in myocardial and mitral valve dysfunction J Am Coll Cardiol 1995;25:305-310.[Abstract] 39. Beppu S, Suzuki S, Matsuda H, Ohmori F, Nagata S, Miyatake K. Rapidity of progression of aortic stenosis in patients with congenital bicuspid aortic valves Am J Cardiol 1993;71:322-327.[CrossRef][Web of Science][Medline] 40. Ross Jr. J, Braunwald E. Aortic stenosis Circulation 1968;38:61-67.[Medline] 41. Wood P. Aortic stenosis Am J Cardiol 1958;1:553-571.[CrossRef][Web of Science][Medline] 42. Pellikka PA, Nishimura RA, Bailey KR, Tajik AJ. The natural history of adults with asymptomatic, hemodynamically significant aortic stenosis J Am Coll Cardiol 1990;15:1012-1017.[Abstract] 43. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997;95:2262-2270.[Abstract/Free Full Text] 44. Cheitlin MD, Armstrong WF, Aurigemma GP, et al. ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography–summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography) J Am Coll Cardiol 2003;42:954-970.[Free Full Text] 45. Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography J Am Soc Echocardiogr 2002;15:167-184.[CrossRef][Web of Science][Medline] 46. Otto CM. Valvular aortic stenosis: disease severity and timing of intervention J Am Coll Cardiol 2006;47:2141-2151.[Abstract/Free Full Text] 47. Skjaerpe T, Hegrenaes L, Hatle L. Noninvasive estimation of valve area in patients with aortic stenosis by Doppler ultrasound and two-dimensional echocardiography Circulation 1985;72:810-818.[Abstract/Free Full Text] 48. Pibarot P, Dumesnil JG. Assessment of aortic stenosis severity: check the valve but don't forget the arteries! Heart 2007;93:780-782.[Free Full Text] 49. Kadem L, Dumesnil JG, Rieu R, Durand LG, Garcia D, Pibarot P. Impact of systemic hypertension on the assessment of aortic stenosis Heart 2005;91:354-361.[Abstract/Free Full Text] 50. Currie PJ, Seward JB, Reeder GS, et al. Continuous-wave Doppler echocardiographic assessment of severity of calcific aortic stenosis: a simultaneous Doppler-catheter correlative study in 100 adult patients Circulation 1985;71:1162-1169.[Abstract/Free Full Text] 51. Baumgartner H, Stefenelli T, Niederberger J, Schima H, Maurer G. "Overestimation" of catheter gradients by Doppler ultrasound in patients with aortic stenosis: a predictable manifestation of pressure recovery J Am Coll Cardiol 1999;33:1655-1661.[Abstract/Free Full Text] 52. Ge S, Warner Jr. JG, Abraham TP, et al. Three-dimensional surface area of the aortic valve orifice by three-dimensional echocardiography: clinical validation of a novel index for assessment of aortic stenosis Am Heart J 1998;136:1042-1050.[CrossRef][Web of Science][Medline] 53. Goland S, Trento A, Iida K, et al. Assessment of aortic stenosis by three-dimensional echocardiography: an accurate and novel approach Heart 2007;93:801-807.[Abstract/Free Full Text] 54. Kasprzak JD, Nosir YF, Dall'Agata A, et al. Quantification of the aortic valve area in three-dimensional echocardiographic data sets: analysis of orifice overestimation resulting from suboptimal cut-plane selection Am Heart J 1998;135:995-1003.[CrossRef][Web of Science][Medline] 55. Menzel T, Mohr-Kahaly S, Kolsch B, et al. Quantitative assessment of aortic stenosis by three-dimensional echocardiography J Am Soc Echocardiogr 1997;10:215-223.[CrossRef][Web of Science][Medline] 56. Alkadhi H, Wildermuth S, Plass A, et al. Aortic stenosis: comparative evaluation of 16-detector row CT and echocardiography Radiology 2006;240:47-55.[Abstract/Free Full Text] 57. Pouleur AC, le Polain de Waroux JB, Pasquet A, Vanoverschelde JL, Gerber BL. Aortic valve area assessment: multidetector CT compared with cine MR imaging and transthoracic and transesophageal echocardiography Radiology 2007;244:745-754.[Abstract/Free Full Text] 58. John AS, Dill T, Brandt RR, et al. Magnetic resonance to assess the aortic valve area in aortic stenosis: how does it compare to current diagnostic standards? J Am Coll Cardiol 2003;42:519-526.[Abstract/Free Full Text] 59. Malyar NM, Schlosser T, Barkhausen J, et al. Assessment of aortic valve area in aortic stenosis using cardiac magnetic resonance tomography: comparison with echocardiography Cardiology 2008;109:126-134.[CrossRef][Web of Science][Medline] 60. Pouleur AC, le Polain de Waroux JB, Pasquet A, Vancraeynest D, Vanoverschelde JL, Gerber BL. Planimetric and continuity equation assessment of aortic valve area: head to head comparison between cardiac magnetic resonance and echocardiography J Magn Reson Imaging 2007;26:1436-1443.[CrossRef][Web of Science][Medline] 61. Tanaka K, Makaryus AN, Wolff SD. Correlation of aortic valve area obtained by the velocity-encoded phase contrast continuity method to direct planimetry using cardiovascular magnetic resonance J Cardiovasc Magn Reson 2007;9:799-805.[CrossRef][Web of Science][Medline] 62. Caruthers SD, Lin SJ, Brown P, et al. Practical value of cardiac magnetic resonance imaging for clinical quantification of aortic valve stenosis: comparison with echocardiography Circulation 2003;108:2236-2243.[Abstract/Free Full Text] 63. Bruch C, Stypmann J, Grude M, Gradaus R, Breithardt G, Wichter T. Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis: clinical usefulness and diagnostic accuracy Am Heart J 2004;148:696-702.[CrossRef][Web of Science][Medline] 64. Giorgi D, Di Bello V, Talini E, et al. Myocardial function in severe aortic stenosis before and after aortic valve replacement: a Doppler tissue imaging study J Am Soc Echocardiogr 2005;18:8-14.[CrossRef][Web of Science][Medline] 65. Galema TW, Yap SC, Geleijnse ML, et al. Early detection of left ventricular dysfunction by Doppler tissue imaging and N-terminal pro-B-type natriuretic peptide in patients with symptomatic severe aortic stenosis J Am Soc Echocardiogr 2008;21:257-261.[CrossRef][Web of Science][Medline] 66. Van Pelt NC, Stewart RA, Legget ME, et al. Longitudinal left ventricular contractile dysfunction after exercise in aortic stenosis Heart 2007;93:732-738.[Abstract/Free Full Text] 67. Iwahashi N, Nakatani S, Kanzaki H, Hasegawa T, Abe H, Kitakaze M. Acute improvement in myocardial function assessed by myocardial strain and strain rate after aortic valve replacement for aortic stenosis J Am Soc Echocardiogr 2006;19:1238-1244.[CrossRef][Web of Science][Medline] 68. Nagel E, Stuber M, Burkhard B, et al. Cardiac rotation and relaxation in patients with aortic valve stenosis Eur Heart J 2000;21:582-589.[Abstract/Free Full Text] 69. Biederman RW, Doyle M, Yamrozik J, et al. Physiologic compensation is supranormal in compensated aortic stenosis: does it return to normal after aortic valve replacement or is it blunted by coexistent coronary artery disease? An intramyocardial magnetic resonance imaging study Circulation 2005;112:I429-I436.[Web of Science][Medline] 70. Van Der Toorn A, Barenbrug P, Snoep G, et al. Transmural gradients of cardiac myofiber shortening in aortic valve stenosis patients using MRI tagging Am J Physiol Heart Circ Physiol 2002;283:H1609-H1615.[Abstract/Free Full Text] 71. Omar RZ, Ambler G, Royston P, Eliahoo J, Taylor KM. Cardiac surgery risk modeling for mortality: a review of current practice and suggestions for improvement Ann Thorac Surg 2004;77:2232-2237.[Abstract/Free Full Text] 72. Romhilt DW, Estes Jr EH. A point-score system for the ECG diagnosis of left ventricular hypertrophy Am Heart J 1968;75:752-758.[CrossRef][Web of Science][Medline] 73. Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis Eur Heart J 2005;26:1309-1313.[Abstract/Free Full Text] 74. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale Circulation 1981;64:1227-1234.[Abstract/Free Full Text] 75. Bergler-Klein J, Klaar U, Heger M, et al. Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis Circulation 2004;109:2302-2308.[Abstract/Free Full Text] 76. Jette AM, Davies AR, Cleary PD, et al. The Functional Status Questionnaire: reliability and validity when used in primary care J Gen Intern Med 1986;1:143-149.[Web of Science][Medline] 77. Bermejo J, Odreman R, Feijoo J, Moreno MM, Gomez-Moreno P, Garcia-Fernandez MA. Clinical efficacy of Doppler-echocardiographic indices of aortic valve stenosis: a comparative test-based analysis of outcome J Am Coll Cardiol 2003;41:142-151.[Abstract/Free Full Text] 78. Amato MC, Moffa PJ, Werner KE, Ramires JA. Treatment decision in asymptomatic aortic valve stenosis: role of exercise testing Heart 2001;86:381-386.[Abstract/Free Full Text] 79. Lancellotti P, Lebois F, Simon M, Tombeux C, Chauvel C, Pierard LA. Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis Circulation 2005;112:I377-I382.[Web of Science][Medline] 80. Messika-Zeitoun D, Aubry MC, Detaint D, et al. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography Circulation 2004;110:356-362.[Abstract/Free Full Text] 81. Feuchtner GM, Muller S, Grander W, et al. Aortic valve calcification as quantified with multislice computed tomography predicts short-term clinical outcome in patients with asymptomatic aortic stenosis J Heart Valve Dis 2006;15:494-498.[Web of Science][Medline] 82. Douglas PS, Khandheria B, Stainback RF, et al. ACCF/ASE/ACEP/ASNC/SCAI/SCCT/SCMR 2007 appropriateness criteria for transthoracic and transesophageal echocardiography J Am Coll Cardiol 2007;50:187-204.[Free Full Text] 83. Antonini-Canterin F, Huang G, Cervesato E, et al. Symptomatic aortic stenosis: does systemic hypertension play an additional role? Hypertension 2003;41:1268-1272.[Abstract/Free Full Text] 84. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology Eur Heart J 2007;28:230-268.[Free Full Text] 85. Lund O. Preoperative risk evaluation and stratification of long-term survival after valve replacement for aortic stenosis. Reasons for earlier operative intervention. Circulation 1990;82:124-139.[Abstract/Free Full Text] 86. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease Eur Heart J 2003;24:1231-1243.[Abstract/Free Full Text] 87. Kolh P, Lahaye L, Gerard P, Limet R. Aortic valve replacement in the octogenarians: perioperative outcome and clinical follow-up Eur J Cardiothorac Surg 1999;16:68-73.[Abstract/Free Full Text] 88. Kolh P, Kerzmann A, Lahaye L, Gerard P, Limet R. Cardiac surgery in octogenarians; peri-operative outcome and long-term results Eur Heart J 2001;22:1235-1243.[Abstract/Free Full Text] 89. Akins CW, Daggett WM, Vlahakes GJ, et al. Cardiac operations in patients 80 years old and older Ann Thorac Surg 1997;64:606-614discussion 614–5.[Abstract/Free Full Text] 90. Kolh P, Kerzmann A, Honore C, Comte L, Limet R. Aortic valve surgery in octogenarians: predictive factors for operative and long-term results Eur J Cardiothorac Surg 2007;31:600-606.[Abstract/Free Full Text] 91. Bose AK, Aitchison JD, Dark JH. Aortic valve replacement in octogenarians J Cardiothorac Surg 2007;2:33.[CrossRef][Medline] 92. Urso S, Sadaba R, Greco E, et al. One-hundred aortic valve replacements in octogenarians: outcomes and risk factors for early mortality J Heart Valve Dis 2007;16:139-144.[Web of Science][Medline] 93. Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses Circulation 1994;89:635-641.[Abstract/Free Full Text] 94. Florath I, Albert A, Rosendahl U, Alexander T, Ennker IC, Ennker J. Mid term outcome and quality of life after aortic valve replacement in elderly people: mechanical versus stentless biological valves Heart 2005;91:1023-1029.[Abstract/Free Full Text] 95. Piper C, Korfer R, Horstkotte D. Prosthetic valve endocarditis Heart 2001;85:590-593.[Free Full Text] 96. Anttila V, Heikkinen J, Biancari F, et al. A retrospective comparative study of aortic valve replacement with St. Jude medical and medtronic-hall prostheses: a 20-year follow-up study. Scand Cardiovasc J 2002;36:53-59.[CrossRef][Web of Science][Medline] 97. Lund O, Bland M. Risk-corrected impact of mechanical versus bioprosthetic valves on long-term mortality after aortic valve replacement J Thorac Cardiovasc Surg 2006;132:20-26.[Abstract/Free Full Text] 98. McKay RG. The Mansfield Scientific Aortic Valvuloplasty Registry: overview of acute hemodynamic results and procedural complications J Am Coll Cardiol 1991;17:485-491.[Abstract] 99. Block PC, Palacios IF. Clinical and hemodynamic follow-up after percutaneous aortic valvuloplasty in the elderly Am J Cardiol 1988;62:760-763.[CrossRef][Web of Science][Medline] 100. Vahanian A, Alfieri OR, Al-Attar N, et al. Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Eur J Cardiothorac Surg 2008;34:1-8.[Abstract/Free Full Text] 101. Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) J Am Coll Cardiol 2002;39:542-553.[Free Full Text] 102. Nkomo VT, Enriquez-Sarano M, Ammash NM, et al. Bicuspid aortic valve associated with aortic dilatation: a community-based study Arterioscler Thromb Vasc Biol 2003;23:351-356.[Abstract/Free Full Text] 103. Subramanian R, Olson LJ, Edwards WD. Surgical pathology of pure aortic stenosis: a study of 374 cases Mayo Clin Proc 1984;59:683-690.[Web of Science][Medline] 104. Michelena HI, Desjardins VA, Avierinos JF, et al. Natural history of asymptomatic patients with normally functioning or minimally dysfunctional bicuspid aortic valve in the community Circulation 2008;117:2776-2784.[Abstract/Free Full Text] 105. Larson EW, Edwards WD. Risk factors for aortic dissection: a necropsy study of 161 cases Am J Cardiol 1984;53:849-855.[CrossRef][Web of Science][Medline] 106. Monin JL, Quere JP, Monchi M, et al. Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics Circulation 2003;108:319-324.[Abstract/Free Full Text] 107. Quere JP, Monin JL, Levy F, et al. Influence of preoperative left ventricular contractile reserve on postoperative ejection fraction in low-gradient aortic stenosis Circulation 2006;113:1738-1744.[Abstract/Free Full Text] 108. Bergler-Klein J, Mundigler G, Pibarot P, et al. B-type natriuretic peptide in low-flow, low-gradient aortic stenosis: relationship to hemodynamics and clinical outcome: results from the Multicenter Truly or Pseudo-Severe Aortic Stenosis (TOPAS) study Circulation 2007;115:2848-2855.[Abstract/Free Full Text] 109. Monin JL, Monchi M, Gest V, Duval-Moulin AM, Dubois-Rande JL, Gueret P. Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low-dose dobutamine echocardiography J Am Coll Cardiol 2001;37:2101-2107.[Abstract/Free Full Text] 110. Carabello BA. Aortic stenosis: two steps forward, one step back Circulation 2007;115:2799-2800.[Free Full Text] 111. Flachskampf FA. Severe aortic stenosis with low gradient and apparently preserved left ventricular systolic function—under-recognized or overdiagnosed? Eur Heart J 2008;29:966-968.[Free Full Text] 112. Minners J, Allgeier M, Gohlke-Baerwolf C, Kienzle RP, Neumann FJ, Jander N. Inconsistencies of echocardiographic criteria for the grading of aortic valve stenosis Eur Heart J 2008;29:1043-1048.[Abstract/Free Full Text] 113. Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival Circulation 2007;115:2856-2864.[Abstract/Free Full Text]
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R. Goel, P. P. Sengupta, F. Mookadam, H. P. Chaliki, B. K. Khandheria, and A. J. Tajik
Valvular regurgitation and stenosis: when is surgery required?
Heart Asia,
July 5, 2010;
1(1):
20 - 25.
[Abstract]
[Full Text]
[PDF]
|
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C. D. Steadman, S. Ray, L. L. Ng, and G. P. McCann
Natriuretic Peptides in Common Valvular Heart Disease
J. Am. Coll. Cardiol.,
May 11, 2010;
55(19):
2034 - 2048.
[Abstract]
[Full Text]
[PDF]
|
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|
|
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D. H. Kang, S. J. Park, J. H. Rim, S. C. Yun, D. H. Kim, J. M. Song, S. J. Choo, S. W. Park, J. K. Song, J. W. Lee, et al.
Early Surgery Versus Conventional Treatment in Asymptomatic Very Severe Aortic Stenosis
Circulation,
April 6, 2010;
121(13):
1502 - 1509.
[Abstract]
[Full Text]
[PDF]
|
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F. G. Bakaeen, D. Chu, M. Ratcliffe, R. R. Gopaldas, A. S. Blaustein, R. Venkat, J. Huh, S. A. LeMaire, J. S. Coselli, and B. A. Carabello
Severe Aortic Stenosis in a Veteran Population: Treatment Considerations and Survival
Ann. Thorac. Surg.,
February 1, 2010;
89(2):
453 - 458.
[Abstract]
[Full Text]
[PDF]
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E. E. Coglianese and R. Davidoff
Predicting Outcome in Patients With Asymptomatic Aortic Stenosis
Circulation,
July 7, 2009;
120(1):
9 - 11.
[Full Text]
[PDF]
|
|
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E. L. Hannan, Z. Samadashvili, S. J. Lahey, C. R. Smith, A. T. Culliford, R. S.D. Higgins, J. P. Gold, and R. H. Jones
Aortic Valve Replacement for Patients With Severe Aortic Stenosis: Risk Factors and Their Impact on 30-Month Mortality
Ann. Thorac. Surg.,
June 1, 2009;
87(6):
1741 - 1749.
[Abstract]
[Full Text]
[PDF]
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Abstract
Calcific Aortic Valve Disease:...