Definition of severe aortic stenosis: ‘A wise man points at the moon, the fool looks at the finger’ (Chinese proverb)

This editorial refers to ‘Progression of aortic stenosis and echocardiographic criteria for its severity’ by K. Kebed et al., pp. 737–743. In the last few years, the definition of severe aortic stenosis (AS) has become a frequent subject of debate. Whilst transthoracic echocardiography is still considered the key diagnostic tool for the diagnosis and classification of AS, a multimodality imaging approach, including dobutamine stress echocardiography, and aortic valve calcium scoring on computed tomography (CT), is proposed for patients with discordant echocardiographic assessments of disease severity [most commonly an aortic valve area (AVA) <1.0 cm2 and mean aortic pressure gradient (MPG) <40 mmHg].1 Another important issue in the management of AS is the rate of progression of the disease. Assessments of valve calcification on CT and positron emission tomography have demonstrated their ability to identify subjects at increased risk of AS progression; however, the influence of AS phenotypes, gender, race, cardiovascular risk factors, genetics, and concomitant comorbidities remains incompletely understood.2 The classical cut-offs proposed by the European and American guidelines3,4 for the identification of severe AS include a maximal aortic velocity (Vmax) ≥ 4 m/s, MPG ≥ 40 mmHg, and AVA ≤ 1 cm2 (or ≤0.6 cm2/m2). Nevertheless, these recommendations acknowledge the fact that there is not only one phenotype of AS. Patients with impaired left ventricular ejection fraction (LVEF) can have severe low gradient (MPG < 40 mmHg) AS because of a reduction in LV stroke volume (classical low flow AS). Moreover, Hachicha et al.,5 showed that patients with low gradient (MPG <40 mmHg) AS and preserved LVEF could have an AVA ≤1 cm2 and a dismal prognosis, often in the context of a small ventricle or mitral regurgitation leading to low stroke volume (paradoxical low flow AS). Their data, together with other succeeding studies,6,7 have led to the development of a more complex classification of AS severity according to LVEF, LV stroke volume index (SVi), and MPG (Figure 1). Summary of the phenotypes of aortic valve stenosis and the corresponding indication to treatment. Summary of the phenotypes of aortic valve stenosis and the corresponding indication to treatment. Some patients with low gradient AS and preserved LVEF have small LV cavity, significant LV hypertrophy, depressed LV longitudinal function, and sometimes a restrictive physiology which might easily justify the concomitant reduction in SVi (<35 mL/m2) the poor outcome and the need for aortic valve replacement (AVR) (Class IIA, level of evidence B in European recommendations). On the other hand, the management of patients with low gradient severe AS, preserved LVEF, and normal SVi (≥35 mL/m2) remains an object of debate. Some studies show that patients with low gradient AS and preserved EF have a prognosis which is similar to that observed in moderate AS.8,9 In other retrospective series, these patients have irreversible myocardial fibrosis and a poor outcome,5,6,10 which means that this subtype of AS is heterogeneous and not always a benign disease, underscoring the need for prospective studies aimed at assessing the benefit of AVR vs. clinical follow-up in this cohort.11 Moreover, in a large cohort of 16.129 with AS, Strange et al.12 have shown that the prognosis of patients with moderate AS according to the classic criteria is more similar to that of patients with severe AS. This may reflect the importance of the hypertrophic response in governing patient outcomes and might represent a first step forward a shifting of paradigm in the management of this AS in population generally considered at ‘lower risk’. This direction is facilitated by the increasing important role of transcatheter aortic valve replacement, which has significantly reduced mobility and mortality in high and probably also medium risk patients.13 In this complex landscape, the paper of Kebed et al.14 is to be congratulated providing us with large scale, real-life data on both patients with discordant AS and the natural evolution of this disease. First Kebed et al.,14 have demonstrated that male sex and Caucasian race are important factors associated with more rapid AS progression. Whilst this is important and deserves specific consideration, we think that the main merit of this manuscript is to renew the debate on the classification of AS severity and to underscore the inconsistency of current diagnostic criteria for AS in a large cohort of patients with moderate-to-severe AS. In a previous study on 333 patients with moderate-to-severe AS undergoing echocardiography and cardiac catheterization, Minners et al.15 have already underscored the inconsistency between the AVA end MPG cut-off proposed in recommendations. These inconsistencies persisted at cardiac catheterization and were identified also in patients with preserved SVi. In their work, Kebed et al. applied the Gorlin formula to data directly obtained from patients in order to correlate AVA, Vmax, and MPG. Despite the intrinsic limitation of their method, which relies essentially on the use of fixed reference values for cardiac output, heart rate, and systolic ejection period, Kebed et al. were able to demonstrate that an AVA of 1.0 cm2 corresponds to an MPG of 32 mmHg and to an aortic Vmax of 3.7 m/s.14 Conversely, an MPG of 40 mmHg and a Vmax of 4 m/s, corresponds respectively to an AVA of 0.89 cm2 and 0.92 cm2. The results of Kebed et al. suggest that the current debate on AS severity might be solved by the application of haemodynamic criteria (the Gorlin formula) to echocardiographic derived data. On one side, their results provide a pathophysiological explanation for the discordant echocardiographic findings observed in some patients particularly those with normal stroke volumes. On the other hand, these data do not take into account the ‘dynamic nature’ of AS parameters, which are largely influenced by change in LV afterload or LV flow rate.16 Whilst they show that the discrepancies observed between AVA, Vmax, and MPG are particularly evident in patients with reduced SVi and/or LVEF, it is not clear if this discordance might have been solved by a careful consideration of transaortic flow rate on stress echocardiography.1,11 Moreover, these results do not identify whether patients with discordant measurements actually have moderate or severe disease and they do not consider the role that simple measurement errors might have played at the time of echocardiography. The importance of a comprehensive and meticulous approach to the echocardiographic assessment of AS severity is paramount and must not be overlooked. This includes careful measurement of the aortic annulus, the application of a multi-window approach for the estimation of maximal aortic velocity and gradients and the use—when deemed necessary—of a multimodality imaging approach to adjudicate disease severity. As with all real-world observational data, the results presented with Kebed et al. have limitations however with confirmation in multicentric and prospective studies, they might contribute to an important turning point for the future classification and management of AS.14 Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of EHJCI, the European Heart Rhythm Association or the European Society of Cardiology.