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cardiomyopathy] may help to optimize medical treatment before and after valve intervention.285,286 Current European recommendations for the echocardiographic grading of AS rely on measurement of the mean pressure gradient (most robust parameter), peak transvalvular velocity (Vmax), and effective AVA. Although AVA is theoretically the ideal parameter for assessing severity, there are numerous technical limitations associated with its calculation.284,287 Aortic stenosis may be further categorized according to flow state based on stroke volume index (SVi) when there is discordance between echocardiographic parameters (Figure 6). A threshold of 35 mL/m2 is conventionally accepted to discern low from normal flow, although sex-specific thresholds have been proposed.292

Concordant criteria: • High-gradient AS [mean gradient ≥40 mmHg, Vmax ≥4.0 m/s, AVA ≤1 cm2 (or ≤0.6 cm2/m2)] is considered severe irrespective of LV function and flow conditions.

Discordant criteria: • Low-flow, low-gradient AS with reduced LVEF (mean gradient <40 mmHg, AVA ≤1 cm2, SVi ≤35 mL/m2, LVEF <50%). • Low-flow, low-gradient AS with preserved LVEF (mean gradient <40 mmHg, AVA ≤1 cm2, SVi ≤35 mL/m2, LVEF ≥50%). • Normal-flow, low-gradient AS with preserved EF (mean gradient <40 mmHg, AVA ≤1 cm2, SVi >35 mL/m2, LVEF ≥50%). • Discordant high-gradient AS (mean gradient ≥40 mmHg, AVA >1 cm2).

Patients with discordant normal-flow, low-gradient AS usually have moderate stenosis.293–295 Discordant high-gradient AS is considered severe if not caused by a reversible high-flow status.296–298 In patients with low-flow, low-gradient AS with reduced LVEF, dobutamine stress echocardiography (DSE) can help to discriminate between pseudo-severe and true severe AS in the presence of flow reserve (increase in stroke volume of ≥20%).289,299 Cardiac computed tomography calcium AV scoring is readily available and provides important adjunctive information in patients with low-flow, low-gradient AS because it correlates with haemodynamic severity, progression, and clinical outcomes.300,301 Values of >2000 Agatston units (AU) in men and >1200 AU in women indicate severe AS with high sensitivity and specificity (∼85%).302,303 While higher thresholds (men >3000 AU, women >1600 AU) are very specific, severe AS becomes unlikely in patients with calcium AV scoring of <1600 AU in men and <800 AU in women.284,302,303 Cautious interpretation is required in patients who can develop severe AS without pronounced AV calcification such as in BAV, concomitant amyloidosis, and predominantly fibrotic stenosis associated with post-rheumatic, radiation-induced and inflammatory disease.304–308 In low-flow, low gradient AS with reduced LVEF, CCT AV calcium scoring and DSE provide complementary information. If findings are equivocal, an integrated assessment considering all available clinical, morphological, and haemodynamic factors is required.

8.2.2 Additional diagnostic and prognostic

parameters The ratio of the LVOT to the AV Doppler jet velocity time integral (VTI, dimensionless index or velocity ratio) does not require calculation of LVOT area and may assist evaluation when other parameters are equivocal (<0.25 suggests that severe AS is highly likely).309

Assessment of GLS can be useful for risk stratification310 and evaluation of extravalvular cardiac damage.311,312 It provides additional information regarding LV function and a threshold of −15% may contribute to identifying patients with severe asymptomatic AS at increased risk of clinical deterioration or premature mortality.59 Estimated valvuloarterial impedance has been shown to be prognostic of adverse clinical outcomes before and after valve replacement.313–315 Transoesophageal echocardiography (TOE) allows morphological evaluation of the valve, planimetry of AVA and assessment of potential subvalvular obstruction (unless there is acoustic shadowing caused by calcification), and evaluation of concomitant valve disease, and can be of value for peri-procedural imaging in challenging clinical or anatomical scenarios.316 Natriuretic peptides can be used to arbitrate the sources of symptoms in patients with multiple potential causes and help to identify those with high-risk asymptomatic AS who may benefit from early intervention.97,317 Exercise testing can unmask symptoms and haemodynamic intolerance (fall in BP >20 mm Hg) and is recommended for risk stratification in asymptomatic patients with severe AS.102,318 Exercise echocardiography may provide additional prognostic information by assessing the increase in mean pressure gradient and change in LV function.319 Cardiopulmonary exercise testing, eventually complemented by echocardiography, can help to uncover cardiac dysfunction in asymptomatic patients, discriminate cardiac from pulmonary limitation or deconditioning in patients with non-specific symptoms, and inform risk stratification.105,106,320,321 Cardiac magnetic resonance is used to identify altered global LV geometry due to remodelling, as well as to quantify myocardial scarring and diffuse fibrosis, which are associated with the occurrence of adverse events.322–324 Transthyretin cardiac amyloidosis may coexist with AS in elderly patients and the two conditions may causally interrelate.325 When transthyretin cardiac amyloidosis is suspected, the presence of monoclonal protein in serum and urine should be excluded using immunofixation and quantitative determination of free light chains, and diagnosis ascertained by means of diphosphonate scintigraphy.326 Despite the limited long-term prognosis associated with cardiac transthyretin amyloidosis, patients with concomitant severe AS usually benefit from valve intervention.327 LV catheterization is not recommended unless there are symptoms and signs of severe AS, and non-invasive investigations are inconclusive.

8.2.3 Procedural planning

Cardiac computed tomography is key to determining suitability for TAVI and planning the procedure. It is the preferred imaging tool to assess AV anatomy including annulus size, dimensions of the aortic root and ascending aorta, the extent and distribution of valve and LVOT calcification, the distance of coronary ostia from the annular plane, optimal fluoroscopic projections for transcatheter valve deployment, and the feasibility of vascular access.49,328,329 Transoesophageal echocardiography (TOE), which is more operatordependent and does not allow assessment of coronary and peripheral vascular anatomy, or CMR may be considered when CCT is difficult to interpret or relatively contraindicated (e.g. in patients with renal failure).330,331

8.3 Medical therapy

No medical therapies have been shown to influence the natural history of AS to date. Neither statins, which demonstrated favourable effects in pre-clinical studies,332–334 nor substances

ESC Guidelines                                                                                                                                                                                          4663

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