Normal-flow low-gradient severe aortic stenosis is a frequent and real entity

This editorial refers to ‘The impact of aortic valve replacement on survival in patients with normal flow low gradient severe aortic stenosis: a propensity-matched comparison’, by S. Saeed et al., pp. 1094–1101. Low-gradient aortic stenosis (AS) [i.e. an aortic valve area (AVA) <1 cm2 with a mean transvalvular gradient <40 mmHg and/or peak jet aortic velocity <4 m/s] is a frequent finding, with up to 40% AS patients harbouring discrepant results at transthoracic echocardiography (TTE) examination.1 This discordant grading pattern raises challenges and uncertainties regarding the true severity of the valve disease. Therefore, a thorough, integrative approach including assessment of flow status has been proposed in recent guidelines.2 According to guidelines, the presence of a low ‘flow’ [i.e. a stroke volume index (SVi) <35 mL/m2] with either a depressed (‘classical’) or preserved (‘paradoxical’) left ventricular ejection fraction (LVEF) increases the likelihood of a true-severe AS (because of the well-known known flow-dependency of mean gradient3). Hence, a multimodality imaging approach through multidetector computed tomography (MDCT) has been proposed1,2 in order to assess the anatomic AS severity and guide therapeutic decision making. In the presence of a normal flow (i.e. SVi ≥35 mL/m2), the guidelines state: ‘if normal flow and low gradient are confirmed, these patients will, in general, not have severe AS and do not benefit from intervention’.2 The concept that normal-flow low-gradient (NF-LG) pattern implies the presence of a non-severe AS is still advocated by many authors.4–6 There is, however, strong evidence that a significant proportion of patients with NF-LG AS patients actually have true severe AS with ensuing adverse prognosis and therefore significantly benefit from aortic valve replacement (AVR).7–10 From a pathophysiological and fluid dynamics standpoint and after excluding measurement errors and the inherent inconsistencies in guidelines AS severity criteria, the presence of a low-gradient despite a normal SVi explained by several factors7,11 (Figure 1). The first and more obvious is the presence of a low transvalvular flow rate (FR) (volume of fluid that passes per unit time and measured by TTE as the stroke volume divided by the left ventricle ejection time12) despite a normal SVi, such as may occur in patients with bradycardia and prolonged left ventricular ejection time.7 Therefore, there is growing interest in assessing the prognostic value of FR in AS.12 The group of Royal Brompton Hospital has recently shown that FR provides incremental prognostic value beyond clinical risk factors, LVEF and even SVi13 in a population of severe AS patients undergoing AVR. The other main factor affecting the AVA gradient relationship and leading to a NF-LG pattern despite the presence of severe AS is abnormal arterial haemodynamics: the presence of systemic hypertension and reduced arterial compliance has been shown to decrease SVi, prolong left ventricular ejection time, and may also blunt the transvalvular gradients and velocities by the faster and earlier reflection of arterial wave.7,14 Pathophysiology and diagnostic workup of paradoxical low–low flow and normal-flow, low-gradient aortic stenosis. This figure shows the potential causes leading to paradoxical low-flow and normal-flow low-gradient aortic stenosis and a proposed algorithm for the diagnostic workup of patients with NF-LG AS (adapted from Clavel et al.7). In the elegant study published by Saeed et al.,15 AVR was associated with decreased mortality in patients with NF-LG symptomatic ‘presumed’ severe AS on the basis of an aortic valve area <1 cm2. This first finding is of uttermost importance for patient management and further underlines that a substantial proportion of patients with bona fide NF-LG have true severe AS and benefit from AVR. Hence according to the present study as well as several previous studies, a multimodality imaging approach should be considered to confirm AS severity and indication of intervention in any symptomatic patient with discordant grading at echocardiography, regardless of the LVEF and flow status. Nevertheless, flow status should still be assessed given that a decreased SVi is a strong predictor of worse outcome. In the present study, the second conclusion regarding the superiority of FR over SVi for prognostic assessment is less sound. Though a recent publication from the same group provides evidence of the incremental prognostic value of FR over SVi13 and absolute numbers favour FR as compared to SVi [e.g. a hazard ratio of survival of 6.28 (3.34–13.16) vs. 3.83 (2.30–6.37), respectively], the present study was neither designed nor powered to prove the superiority of one marker over another. Either way, it is reassuring that results are consistent, independently of the definition of low flow used. Finally, the study confirms previous reports that LVEF >50% may not be normal in AS and that patients with LVEF in the lower normal range (i.e. 50–54%) have increased mortality.16 This reinforces the urge to revisit the current guideline threshold of 50% for LVEF to define AVR indication.2,17 Several recent studies actually provide support to an increase of LVEF threshold from 50% to 60% in patients with severe AS.16,18,19 The main limitation of the study15 comes from its inherent observational and retrospective nature. However, the use of propensity score matching minimizes the potential bias. Furthermore, the authors did not distinguish between the type of treatment (surgical or transcatheter), which may have an impact on the primary outcome. The inclusion of MDCT aortic valve calcium scoring would have been a desirable addition in this study in order to provide a flow-independent parameter that allowed to confirm anatomical severity. In summary, this elegant study by Saeed et al.15 provides further evidence that an important proportion of patients with NF-LG indeed have true-severe AS and ensuing worse prognosis in the absence of intervention. In such patients, AVR is associated with a significant decrease in mortality. Further research regarding the optimal timing and type (i.e. surgical or transcatheter) of intervention is warranted. This study also provides support to a revision of the guidelines and inclusion of a Class IIa indication of AVR in symptomatic patients with NF-LG severe AS. 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.

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