Echocardiographic assessment of morphology and severity with its pitfalls and limitations
Assessment of morphology
Site of left ventricular outflow obstruction—differential diagnosis
Aortic stenosis (AS) is most commonly valvular. However, left ventricular outflow tract obstruction also occurs subvalvular and can then be either fixed in case of congenital malformation (discrete membrane or muscular band; or dynamic in the case of hypertrophic obstructive cardiomyopathy (see section on Cardiomyopathies) or supravalvular as rare congenital condition. Because of the fundamental differences in treatment strategies it is essential to correctly identify the level of left ventricular outflow tract obstruction. Echocardiography allows distinction of these entities by morphologic assessment, Doppler determination of the site of velocity increase, and analysis of its time course (early, mid, late systolic peak; see Fig. 10.4). Typical examples are shown in Fig. 10.1.
Assessment of AS aetiology
Calcific AS is the most common form and is characterized by thickened and calcified cusps (bicuspid or tricuspid valve) with reduced mobility . Congenital AS presents most commonly with bicuspid and less frequently with unicuspid, tricuspid, or quadricuspid valves. The two cusps of bicuspid valves are typically of different size and the larger cusp often contains a raphe (fusion line of two cusps). Typically the cusps are oriented either in an anterior/posterior (fusion of right and left coronary cusp; 80%) or right/left manner (fusion of right and non-coronary cusp). Rheumatic aortic stenosis is characterized by commissural fusion, thickening of the cusp edges, and sometimes cusp retraction. It is commonly associated with aortic regurgitation and mitral valve involvement. Typical examples are shown in Fig. 10.2. In advanced disease stages, congenitally malformed and rheumatic valves develop calcification. Once the valve is extensively calcified, the exact determination of underlying morphology and aetiology becomes difficult.
Assessment of aortic valve calcification
Aortic valve calcification is best assessed in a short-axis view, although the presence of extensive calcification may also be noted in the 5-chamber view. The degree of calcification (see Fig. 10.3) can be classified into mild (isolated, small spots), moderate (multiple bigger spots), and severe (extensive thickening/calcification of all cusps). It has prognostic implications (see Calcification of the aortic valve) .
Assessment of the aorta
Assessment of the ascending aorta is crucial as aneurysms are not uncommon. In particular, congenital AS is frequently associated with dilatation of the ascending aorta. Its extent is not related to the haemodynamic severity of AS. Dilation at the level of sinuses is in general easily recognized. However, aneurysms distal to the sinotubular junction are more difficult to image and require special care generating atypical long-axis views with angulation towards the ascending aorta.
Quantification of stenosis severity
A normal aortic valve has an orifice area of 3–4 cm2 and a laminar normal transvalvular flow with a peak velocity of less than 2 m/s. While several other parameters have been proposed for the AS quantification, peak transvalvular velocity, mean Doppler gradient, and effective orifice area, as derived from the continuity equation, have been best validated and are currently recommended for clinical assessment of AS [3–5].
Transvalvular velocity and gradients
Transvalvular velocity continuously increases with AS severity as long as cardiac output is maintained.
Transvalvular gradients (ΔP) are calculated from continuous-wave Doppler derived transvalvular velocities (v) using the Bernoulli equation, which is based on the conservation of energy principle. In clinical practice, the simplified Bernoulli equation:
which ignores viscous losses and the effects of flow acceleration, is used . It also ignores the flow velocity proximal to the stenosis, which is an acceptable assumption as long as the transvalvular velocity is significantly greater than the proximal flow velocity and in particular when ≤1 m/s. However, if proximal velocity is increased (narrow outflow tract or increased flow rate caused by high cardiac output or aortic regurgitation) the less simplified version:
should be used, where v2 and v1 represent the transvalvular and the proximal flow velocities, respectively.
The peak transaortic pressure gradient corresponds to the maximum instantaneous difference between the pressure in the aorta and the ventricle. With increasing stenosis severity, the peak of the gradient occurs later during systole (see Fig. 10.4). Note that the peak gradient is different from the ‘peak-to-peak’ gradient that is determined by catheter and corresponds to the difference between peak aortic pressure and peak left ventricular pressure. The latter is not a physiologic measure, since these two peaks do not occur simultaneously and it cannot be determined by Doppler echocardiography.
Technical considerations and pitfalls
Besides the neglect of an increased subvalvular velocity (see gradient calculation) a number of other sources of error may occur. A correct alignment of the Doppler beam with the direction of the stenotic jet is essential. Malalignment leads to an underestimation of the Doppler gradient and hence of the severity of AS. Multiple transducer positions (i.e. right parasternal, suprasternal, apical, and sometimes even subcostal) have to be used, to obtain the accurate velocity. For that purpose, the use of a small, dedicated continuous-wave Doppler transducer (pencil probe) is mandatory (see Fig. 10.5). When the rate of haemodynamic progression is determined, one has to make sure that measurements are recorded from the same window.
Another potential source of error that needs to be avoided is the confusion of the AS signal with a signal originating from another obstruction or from mitral or tricuspid regurgitation. In the presence of arrhythmias, such as atrial fibrillation, several consecutive beats have to be averaged and beats after long R–R intervals or post-extrasystolic beats must be avoided.
The phenomenon of pressure recovery may also cause pitfalls and may explain discrepancies between catheter and Doppler derived pressure gradients . Obstruction of flow in any kind of stenosis causes flow velocity increase and pressure drop corresponding to a conversion of potential energy to kinetic energy. Pressure is lowest and velocity is greatest at the level of the vena contracta, the site of minimum cross-sectional flow area. The jet expands and decelerates downstream from the stenosis. Although some of the kinetic energy dissipates into heat due to turbulences and viscous losses, some of it will be reconverted into potential energy and pressure will increase again to some degree (= pressure recovery). The Doppler gradient corresponds to the maximum pressure drop from proximal to the vena contracta and overestimates the net pressure drop as usually given by catheter measurement in the case of significant pressure recovery. In AS, the magnitude of pressure recovery is frequently small since the abrupt widening from the small valve orifice to a generally normally sized or enlarged aorta causes a lot of turbulence. However, the effects of pressure recovery may be significant in the presence of a small ascending aorta (<30mm) .
Doppler velocites and pressure gradients are highly flow-dependent. In the presence of high cardiac output or significant aortic regurgitation consideration of these measurements alone may cause significant overestimation of AS severity. On the other hand, in the presence of low flow rates, most commonly caused by an impaired left ventricular function but also e.g. in the presence of mitral stenosis or small hypertrophied ventricles, AS severity may be underestimated. Thus, valve area, as a less flow-dependent parameter, is required for appropriate AS quantification.
Valve area calculation by the continuity equation
The continuity equation has gained most acceptance for valve area calculation [8, 9]. It is based on the fact that the stroke volume passing through the left ventricular outflow tract (LVOT) must equal the stroke volume crossing the stenotic aortic valve:
where AVA is the aortic valve area, VTIAS and VTILVOT are the velocity time integrals in the LVOT and effective valve orifice, respectively and CSALVOT is the cross-sectional area of the LVOT (see Fig. 10.6).
A simplified version of the continuity equation that uses peak aortic jet and outflow tract velocities instead of the velocity time integral has also been proposed.
The cross-sectional area (CSA) of the LVOT is calculated using the formula:
where D is the diameter of the LVOT measured in the parasternal long-axis view at mid-systole.
This assumption of a circular LVOT shape (while it is indeed frequently oval) and the requirement of measuring LVOT size and velocity exactly at the same site are important limitations of the method that may cause error.
The LVOT flow velocity is measured from an apical approach using pulsed Doppler ultrasound with the assumption of laminar flow and a flat velocity profile. The fact that these assumptions may not be fulfilled also limits the accuracy of the method.
Despite these limitations, the continuity equation has been shown to be currently the best technique of valve area estimation and yields valuable measurements for AS quantification as a basis for patient decision-making when sources of error are carefully considered.
In order to reduce the error related to LVOT measurements it has been proposed to remove it from the continuity equation. The so determined dimensionless velocity ratio expresses the size of the effective valve area as a proportion of the cross-sectional area of the LVOT:
Both velocity time integrals and peak velocities have been used. Severe stenosis is present when the velocity ratio is 0.25 or less, corresponding to a valve area 25% of normal. To some extent, velocity ratio normalizes for body size because it reflects the ratio of the actual valve area to the expected valve area in each patient, regardless of body size. However, this measurement ignores variability in LVOT size beyond variation in body size and has gained less acceptance for routine use than the combination gradients and continuity equation valve area.
Valve area planimetry
Planimetry of the valve area, primarily by 2D TEE has also been proposed. However, the orifice of a stenotic aortic valve frequently represents a complex 3-dimensional structure that cannot be reliably assessed with a planar 2D-image. The presence of valvular calcification further limits an accurate delineation of the aortic valve orifice. Thus, this method has not been accepted as a routine measurement. Nevertheless, it might be useful in selected patients when additional information is needed .
Three-dimensional echocardiography has been reported to allow valve area planimetry but has not sufficiently been validated yet.
Dobutamine echocardiography is indicated in the setting of low flow–low gradient AS, which is defined by a small calculated valve area (<1.0 cm2), in the presence of a reduced transaortic gradient (<30 to 40 mmHg) and a reduced left ventricular function determined by a low-stroke volume index (<35 mL/m2) . It is performed at a low dobutamine dose that is gradually increased up to a maximum dose of 10–20 μg/kg/min by steps of 5 μg/kg/min per 3–5 min, trying not to exceed a heart rate of 100 beats/min.
It allows the determination of the presence of a contractile reserve or a 20% relative increase in ejection fraction (defined as an increase of stroke volume ≥20%), which has been shown to be of prognostic value. In the presence of a contractile reserve it allows a further differentiation between pseudosevere stenosis (compared to baseline, the gradients remain small, whereas the valve area increases significantly with increasing flow, indicating that AS is non-severe and severely reduced opening passively caused by diminished driving forces) and true severe stenosis (gradients increase, whereas the valve area remains small indicating a fixed small valve orifice with a low gradient caused by secondary LV dysfunction and flow reduction).
Experimental methods of AS quantification
Several additional parameters such as valve resistance, stroke work loss, or the energy loss coefficient have been proposed to quantify aortic stenosis severity. Since their complexity adds sources of error and since they lack solid prognostic validation, they are still considered experimental and not recommended for routine clinical use .
Definition of AS severity
By current recommendations, severity of AS is assessed by combining aortic jet velocity, mean gradient and valve area (see Table 10.1) [3–5]. Because of prognostic implications, the differentiation between severe and non-severe stenosis is of particular importance. In the presence of normal transvalvular flow, severe AS is considered with a peak aortic jet velocity greater than 4 m/s and a mean gradient greater than 40 mmHg. Outcome worsens with increasing velocity and event rates have been shown to be particularly high when peak velocities exceed 5.5 m/s. Current recommendations define severe AS by using a cut-off of <1 cm2 for the valve area. It has also been suggested to index aortic valve area to body surface area (cut-off 0.6 cm2/m2). However, there is no linear relation between body surface area and valve area, and there is particular distortion at the extremes of the spectrum.
Table 10.1 Recommendations for classification of AS severity (3-5) [3-5]
Aortic jet velocity (m/s)
≤ 2.5 m/s
Mean gradient (mmHg)
Indexed AVA (cm2/m2)
Diagnosis of severe AS is easy when peak velocity, mean gradient, and valve area are consistent but becomes a challenge if they are inconsistent, in particular when valve area is less than 1 cm2 but peak velocity less than 4 m/s and mean gradient less than 40 mmHg. One reason for this constellation is a reduced flow in the presence of LV dysfunction. In this situation, ‘classical’ low flow–low gradient AS with reduced ejection fraction (EF) must be assumed and dobutamine echocardiography can help to distinguish between pseudosevere and true severe AS (see section Dobutamine echocardiography). The most challenging finding in clinical practice is a valve area smaller than 1 cm2 with a peak velocity less than 4 m/s and mean gradient less than 40 mmHg, despite normal LV EF. The new entity of severe ‘paradoxical’ low flow–low gradient AS with preserved EF has recently been introduced and refers to patients with hypertrophied, small ventricles resulting in reduced transvalvular flow (stroke volume index <35 ml/m2) despite normal EF [11, 12]. However, this entity has to be diagnosed with particular care since other more frequent reasons for the finding of a small valve area and low gradients in the presence of normal EF have to be excluded. The continuity equation may underestimate the valve area because of flow underestimation caused by the underestimation of the LVOT area when assuming a circular shape while it is indeed oval and other measurement errors . Transoesophageal 3D echocardiography may prove to be useful in measuring the definite LVOT cross-sectional area to obtain more accurate values  ( Fig. 10.6d). Furthermore, it has to be emphasized that current cut-offs for valve area and velocity/gradient are not really consistent to begin with. To generate a mean gradient of 40 mmHg with a normal stroke volume, the valve area must be closer to 0.8 than to 1.0 cm2 [15–17]. Finally, small stature of the patient may be another reason for a small valve area and low gradient in the presence of normal EF. Severe ‘paradoxical’ low flow–low gradient AS with preserved EF has in general been described in elderly patients with hypertrophied ventricles of small volume. Reduced longitudinal LV function and fibrosis were found. However, the vast majority of these patients had a history of hypertension that may have caused the LV pathology [11, 12]. In addition, it remains so far unclear how to distinguish between pseudosevere and true severe AS in this setting. Dobutamine echocardiography may be less helpful in these ventricles with small volumes and normal EF. The degree of valve calcification may then be a final important hint to identify true severe AS .
Thus, definition of severe AS remains challenging and current guidelines emphasize that diagnosis in clinical practice must be based on an integrated approach including transvalvular velocity/gradient, valve area, valve morphology, transvalvular velocity, LV morphology and function, blood pressure and symptoms .
Role of MRI and CT
Although echocardiography remains the standard modality for the diagnosis and quantification of AS, MRI and CT are gaining importance, both for valve assessment and adjunct cardiovascular evaluation.
The role of MRI in patients with AS may be 4-fold: (1) assessment of valve morphology, (2) assessment of valve function, (3) assessment of LV function, and (4) assessment of aortic disease.
For the assessment of valve morphology, cine imaging is applied in at least two orthogonal planes through the aortic valve, usually in the orientation of the aortic ring and in the LVOT orientation. Usually cine imaging is performed using steady-state-free-precession sequences with an effective temporal resolution of c. 35 ms. Cine images in LVOT orientation show a flow jet during systole extending from the valve into the ascending aorta. This jet is due to phase dispersion in increased flow velocities. To quantify the aortic valve area by planimetry, systolic images through the aortic ring are needed (see Fig. 10.7). Computer programs are available to perform planimetry semi-automatically on most workstations. Measurements of the aortic valve area based on steady-state free-precession images have been shown to correlate better with TEE than conventional spoiled gradient echo images .
One advantage of MRI (vs. CT) is that in addition to the assessment of valve morphology in cine images, flow can be measured in phase-contrast sequences. The background of these techniques is the fact that the phase shift in moving spins is proportional to their velocity. By measuring the peak velocity one can derive the pressure gradient by the use of the Bernoulli equation (see Fig. 10.7). Prerequisite for exact measurements in phase contrast sequences is that the expected maximum velocity is provided, otherwise aliasing artefacts may occur. Valve area can also be calculated from MRI data using the continuity equation.
MRI is the method of highest accuracy for the assessment of LV function and LV mass. At the same time, the LV can be evaluated for the presence of fibrotic changes by the use of late-enhancement imaging. The detection of diffuse fibrosis has recently been demonstrated using T1 mapping . Pathology of the aorta (aneurysm, coarctation) may be investigated using contrast-enhanced magnetic resonance angiography or 3D cine velocity acquisitions (see Fig. 10.7).
With the advent of 64-slice CT scanners, the assessment of valve morphology and function using CT has become feasible. CT has the advantage of a high spatial resolution and a very high sensitivity for the detection of calcific changes of the valves (see Fig. 10.8). Despite its inferior temporal resolution compared to echo and MRI, CT is able to acquire systolic and diastolic images of the aortic valve that allow for the assessment of valve morphology, as well as planimetry of the aortic valve area (AVA). In recent comparisons of CT and echocardiography, a good correlation of both methods was found with a tendency of CT to measure larger values for AVA [22, 23].
The quantification of valve calcification has been proposed to identify severe AS (>1651 Agatston units: 82% sensitivity, 80% specificity, 88% negative-predictive value and 70% positive-predictive value for the diagnosis of severe AS) in the setting of low flow–low gradient AS  (see Fig. 10.8). While it cannot provide haemodynamic data, CT has the important advantage over MRI and echo that it may also assess the coronary arteries in the same scan. The method has been shown to detect significant coronary artery disease in patients prior to valve surgery .
Prognostic information provided by imaging
Severity of AS
Imaging techniques allow the detection and quantification of AS. Even the presence of aortic sclerosis without haemodynamic obstruction is associated with an increased morbidity and mortality. With an increasing severity of AS, outcome is further impaired. In fact, peak aortic jet velocity is an important predictor of outcome in asymptomatic patients with AS. With increasing velocity, subsequent necessity of an aortic valve replacement becomes more likely  (see Fig. 10.9). A peak velocity >5.5 m/s has been reported to be associated with a particularly high event rate, mostly valve replacement required because of symptom development .
Faster rates of haemodynamic progression are associated with an increased event rate, both in patients with severe, but also in patients with mild-to-moderate, aortic stenosis [2, 26]. Haemodynamic progression is actually indirectly related to AS severity. While there is great inter-individual variability in the rates of haemodynamic progression, the presence of a calcified aortic valve was shown to predict faster haemodynamic progression.
Calcification of the aortic valve
The presence of a moderate-to-severe calcified aortic valve on echocardiography is a significant predictor of outcome in patients with mild-to-moderate AS  (see Fig. 10.10). More importantly, in patients with severe AS, the presence of a moderate-to-severe calcified aortic valve is associated with an event-rate of 80% within 4 years with events defined as symptom onset warranting aortic valve replacement or death  (see Fig. 10.10). The presence of a calcified aortic valve in combination with a rapid haemodynamic progression (defined as an increase in peak aortic jet velocity of more than 0.3 m/s within one year) identifies a high-risk population with an event-rate of 79% within 2 years (see Fig. 10.10).
Left ventricular function
Although LV function has a high tendency to improve after valve replacement, poor LV function is known to be associated with a worse outcome. However, reduced LVEF is extremely rare in asymptomatic patients (<1% of severe AS). A recent study reported a poor outcome of such patients, even after valve replacement, leading to the suspicion that impaired LV function may have been due to other associated yet not identified disease . Global longitudinal LV strain, as measured with echo speckle tracking, may be more sensitive for detecting early LV dysfunction and has been reported to predict events in asymptomatic patients, as well as mortality in aortic stenosis . Furthermore, impaired strain prior to valve replacement has recently been reported to predict worse post-operative outcome with regard to rehospitalization for heart failure and mortality . These new data still require multi-centric validation studies.
Left ventricular hypertrophy
The impact of left ventricular hypertrophy (LVH) on outcome has been studied for a long time with inconclusive results. A recent study reported excessive LVH to be associated with a significantly higher event rate in asymptomatic patients  (see Fig. 10.13).
Focal myocardial fibrosis in AS, as demonstrated by CMR late gadolinium enhancement, has been reported to be associated with worse post-operative outcome in particular residual symptoms but also mortality in patients undergoing valve replacement . Whether the search for fibrosis in asymptomatic patients can help to optimize the time of surgery remains unknown. CMR T1 mapping has recently been reported to identify diffuse fibrosis in AS and can be found even in asymptomatic patients . However, the clinical relevance of such findings remains to be shown.
Pulmonary hypertension (PH) is known to be associated with an increased operative mortality and has therefore been included in current surgical risk scores. PH at rest and with exercise has recently been shown to predict events, mostly symptom development in asymptomatic patients [33, 34].
An exercise-induced increase of the mean transaortic gradient of more than 18mmHg was proposed as a predictor of poor outcome  and this has been confirmed in a second study using a cut-off for the increase in mean gradient of 20 mmHg  (see Fig. 10.11).
Dobutamine echocardiography in low flow–low gradient aortic AS
The absence of contractile reserve in low flow–low gradient aortic stenosis is a predictor of poor outcome  (see Fig. 10.12). When patients with contractile reserve have true severe AS, they generally benefit from aortic valve surgery. However, although they have a markedly higher operative mortality, even patients without contractile reserve may frequently improve in left ventricular function after surgery. A recent study has confirmed that patients with pseudosevere AS followed conservatively have a markedly better outcome than those with true severe AS or without contractile reserve . Management decisions remain difficult in this patient population and need to be taken on an individual basis.
Imaging in clinical decision-making
Indications for surgery
Echocardiography is the gold standard for diagnosis and quantification of AS as the basis for the decision-making process in this disease. The strongest indication for valve replacement is given by the occurrence of symptoms in the presence of severe AS. In asymptomatic patients, otherwise unexplained left ventricular systolic dysfunction, as detected by echo, is considered an indication for surgery [3, 4]. Exercise testing has been shown to be helpful for selecting patients who might benefit from surgery while still reporting to be asymptomatic. The incremental value of exercise echo as compared with regular stress testing still requires validation, although an increase in mean gradient >20 mmHg on exercise has been added as a IIb indication in the recent ESC guidelines and surgery may be considered in asymptomatic patients with low operative risk. The echocardiographically provided criterion of moderate to severe aortic valve calcification and a rapid haemodynamic progression (increase of peak aortic jet velocity >0.3 m/s within 12 months) is a class IIa indication for elective surgery in asymptomatic patients as is a peak velocity >5.5 m/s and surgery should be considered because of a high likelihood of symptom development within a short time. Excessive LVH has also been added as a IIb indication in the recent ESC guidelines and surgery may be considered in asymptomatic patients with low operative risk.
Scheduling follow-up intervals
Intervals for follow-up visits of asymptomatic patients with AS can be scheduled based on the severity of AS. Generally patients with a severe stenosis should be seen every 6 months and patients with moderate AS on a yearly basis. In addition, factors such as the previous rate of haemodynamic progression and the degree valve calcification (important calcification is associated with more rapid disease progression) help to optimize the timing of follow-up visits.
1. 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(7): 920–5.Find this resource:
2. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. NEJM 2000; 343(9): 611–7.Find this resource:
3. 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), Society of Cardiovascular Anesthesiologists, 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; 114, e1–148.Find this resource:
4. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS), Vahanian A, Alfieri O, Andreotti F, Antunes MJ, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012: 2451–96.Find this resource:
5. Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr 2009: 1–23; quiz 101–2.Find this resource:
6. 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(6): 1162–9.Find this resource:
7. 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(6): 1655–61.Find this resource:
8. Otto CM, Pearlman AS, Comess KA, Reamer RP, Janko CL, Huntsman LL. Determination of the stenotic aortic valve area in adults using Doppler echocardiography. JAC 1986; 7(3): 509–17.Find this resource:
9. Oh JK, Taliercio CP, Holmes DR, et al. Prediction of the severity of aortic stenosis by Doppler aortic valve area determination: prospective Doppler-catheterization correlation in 100 patients. JAC 1988; 11(6): 1227–34.Find this resource:
10. Monin J-L, Quéré J-P, 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(3): 319–24.Find this resource:
11. 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(22): 2856–64.Find this resource:
12. Pibarot P, Dumesnil JG. Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction. J Am Coll Cardiol 2012; 60(19): 1845–53.Find this resource:
13. Baumgartner H, Kratzer H, Helmreich G, Kuehn P. Determination of aortic valve area by Doppler echocardiography using the continuity equation: a critical evaluation. Cardiology 1990; 77(2): 101–11.Find this resource:
14. Gaspar T, Adawi S, Sachner R, et al. Three-dimensional imaging of the left ventricular outflow tract: impact on aortic valve area estimation by the continuity equation. J Am Soc Echocardiogr 2012; 25(7): 749–57.Find this resource:
15. Carabello BA. Clinical practice. Aortic stenosis. N Engl J Med 2002; 346(9): 677–82.Find this resource:
16. Minners J, Allgeier M, Gohlke-Baerwolf C, Kienzle R-P, Neumann F-J, Jander N. Inconsistent grading of aortic valve stenosis by current guidelines: haemodynamic studies in patients with apparently normal left ventricular function. Heart 2010; 96(18): 1463–8.Find this resource:
17. Minners J, Allgeier M, Gohlke-Baerwolf C, Kienzle R-P, Neumann F-J, Jander N. Inconsistencies of echocardiographic criteria for the grading of aortic valve stenosis. Eur Heart J 2008; 29(8): 1043–8.Find this resource:
18. Cueff C, Serfaty J-M., Cimadevilla C, et al. Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction. Heart 2011; 97(9): 721–6.Find this resource:
19. Authors Task Force Members, Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012): The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2012, 33, 2451–96.Find this resource:
20. Schlosser T, Malyar N, Jochims M, et al. Quantification of aortic valve stenosis in MRI-comparison of steady-state free precession and fast low-angle shot sequences. Eur Radiol 2007; 17(5): 1284–90.Find this resource:
21. Bull S, White SK, Piechnik SK, et al. Human non-contrast T1 values and correlation with histology in diffuse fibrosis. Heart 2013, 99, 932–7.Find this resource:
22. Lembcke A, Thiele H, Lachnitt A, et al. Precision of forty slice spiral computed tomography for quantifying aortic valve stenosis: comparison with echocardiography and validation against cardiac catheterization. Invest Radiol 2008; 43(10): 719–28.Find this resource:
23. Pouleur A-C, le Polain de Waroux J-B, Pasquet A, Vanoverschelde J-LJ, Gerber BL. Aortic valve area assessment: multidetector CT compared with cine MR imaging and transthoracic and transesophageal echocardiography. Radiology 2007; 244(3): 745–54.Find this resource:
24. Pouleur A-C, le Polain de Waroux J-B, Kefer J, Pasquet A, et al. Usefulness of 40-slice multidetector row computed tomography to detect coronary disease in patients prior to cardiac valve surgery. Eur Radiol 2007; 17(12): 3199–207.Find this resource:
25. Rosenhek R, Zilberszac R, Schemper M, et al. Natural history of very severe aortic stenosis. Circulation 2010; 121(1): 151–6.Find this resource:
26. 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(3): 199–205.Find this resource:
27. Henkel DM, Malouf JF, Connolly HM, et al. Asymptomatic left ventricular systolic dysfunction in patients with severe aortic stenosis: characteristics and outcomes. J Am Coll Cardiol 2012; 60(22): 2325–9.Find this resource:
28. Kearney LG, Lu K, Ord M, et al. Global longitudinal strain is a strong independent predictor of all-cause mortality in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging 2012; 13(10): 827–33.Find this resource:
29. Dahl JS, Videbæk L, Poulsen MK, Rudbæk TR, Pellikka PA, Møller JE. Global strain in severe aortic valve stenosis: relation to clinical outcome after aortic valve replacement. Circ Cardiovasc Imaging 2012; 5(5): 613–20.Find this resource:
30. Cioffi G, Faggiano P, Vizzardi E, et al. Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis. Heart 2011; 97(4): 301–7.Find this resource:
31. Weidemann F, Herrmann S, Störk S, et al. Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation 2009; 120(7): 577–84.Find this resource:
32. Bull S, Suttie JJ, Willis H, et al. Circumferential strain predicts major adverse cardiac events independent of myocardial perfusion in asymptomatic aortic stenosis. J Cardiovasc Magn Reson; 2012 Feb (14), 90.Find this resource:
33. Mutlak D, Aronson D, Carasso S, Lessick J, Reisner SA, Agmon Y. Frequency, determinants and outcome of pulmonary hypertension in patients with aortic valve stenosis. Am J Med. Sci 2012; 343(5): 397–401.Find this resource:
34. Lancellotti P, Magne J, Donal E, et al. Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis. Circulation 2012; 126(7): 851–9.Find this resource:
35. Lancellotti P, Lebois F, Simon M, Tombeux C, Chauvel C, Piérard LA. Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis. Circulation 2005; 112(9 Suppl): I377–82.Find this resource:
36. Maréchaux S, Hachicha Z, Bellouin A et al. Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis. Eur Heart J 2010; 31(11): 1390–7.Find this resource:
37. Fougères E, Tribouilloy C, Monchi M, et al. Outcomes of pseudo-severe aortic stenosis under conservative treatment. Eur Heart J 2012; 33(19): 2426–33.Find this resource:
38. 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(9): 2262–70.Find this resource: