The recently published meta-analysis by Dayan et al. (1) in the Journal evaluated the outcome and survival impact of aortic valve replacement in patients with low-gradient severe aortic stenosis (AS) in patients with preserved left ventricular ejection fraction, including paradoxical low-flow, low-flow low-gradient, normal-flow low-gradient, and those with high-gradient AS or moderate AS. Their meticulous work highlighted a significant mortality benefit in all patients with low-gradient AS, irrespective of their subtype, although comparatively, the highest benefit was observed in patients with classic high gradient AS (1). This obviously brings up an important clinical question which is, “Although it would be intriguing to define the subtype of low-gradient severe AS, but do we really need it to impact our clinical decision for valve replacement referral”?

In particular, the patients’ subgroup of normal-flow low-gradient AS remains of great interest, which in particular has not been addressed in the current guidelines and is less well known to clinicians. The encounter of such patients in practice poses a great clinical dilemma, and the reality is that many clinicians find it mindboggling from a fluid dynamic standpoint to encounter discrepant valve hemodynamic parameters in such patients (2). It is thus not uncommon that the observed echo parameters are often revisited or slightly modified, and even the assistance with additional imaging modalities such as cardiac computed tomography is sorted to reclassify such patients into either moderate or truly severe AS in order to guide the final management strategy. It is thus not surprising that as a result of the same, the patients who have a low-gradient severe (by valve area) AS, are comparatively referred much less often for surgical or transcatheter aortic valve replacement, as even noted in the current meta-analysis (1).

As the authors point out, the normal-flow low-gradient severe AS may be the result of the errors in patients’ measurements of stroke volume, aortic valve area (AVA) or gradient, and/or the result of inconsistent grading criteria (1). It may be indeed true for a large proportion of patients because echocardiography, which is the current accepted standard of routine investigation of AS severity, may suffer from such inherent measurement errors. However, it is generally perceived that invasive hemodynamic values obtained by catheterization data in such patients may yield more concordant hemodynamic values (2). On the contrary, one recent study reported that even 53% of patients with normal-flow, normal ejection fraction have discrepant invasive hemodynamic indices of AS severity, viz. severe AS by valve area (<1 cm2) and low transvalvular gradients (<40 mm Hg) (3). These results suggest that the internal inconsistencies in the proposed AS severity criteria by current guidelines indeed play a major role in the observed discrepancy of hemodynamic parameters in patients with AS (2,3). Carabello (4) has previously demonstrated the potential mismatch of the cutoff values proposed by current guidelines. For instance, a cardiac output of 6 l/min, systolic ejection period of 0.33 s, and heart rate of 80 beats/min, a mean gradient of 26 mm Hg actually yields to an AVA of 1.0 cm2, whereas a mean gradient >40 corresponds with an AVA of 0.8 cm2. Similarly, one striking finding from the prior studies is that the majority of discrepant indices are substantially prevalent when the calculated AVA is between 0.8 and 1.0 cm2, whereas they appear more frequently consistent when the valve area is <0.8 cm2. Moreover, mitral regurgitation is common in elderly AS patients, either as a consequence of left ventricular pressure overload or due to concomitant mitral valve disease (2). In AS patients with concomitant moderate to severe mitral regurgitation, mitral regurgitation may play a confounding role in the causation of a low effective transaortic flow and low transaortic gradient. Thus, accounting the presence of mitral regurgitation in the general clinical assessment may explain the discordance among the observed parameters of AS severity. The AS severity by valve area assessment usually remains unaffected in this setting, as the valve area calculation still remains accurate in this setting (2).

Nevertheless, more data from future randomized controlled investigations are needed to strengthen our understanding about the prognostic long-term outcomes of normal-flow low-gradient AS patients. Secondly, the future guidelines should account for such patients, and indeed, a consideration to revise the definition of severe AS should be made to resolve the discrepancy of hemodynamic parameters in a large proportion of AS patients. Lastly and most importantly, it is high time to realize that such an AS patient population with discrepant hemodynamics truly exists, and their treatment strategy should deserve the same priority as other subtypes. Low-pressure gradient per se as a lone parameter should not affect our treatment referral strategy for the management of such patients!