Response to Letter Regarding Article, “Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis Despite Preserved Ejection Fraction Is Associated With Higher Afterload and Reduced Survival”
We thank Drs Poullis and Warwick for their comments on our article.1 It is evident that the low gradient observed in the patients with paradoxical low flow is due to reduced cardiac output or, more precisely, to reduced stroke volume and transvalvular flow rate. As clearly stated in our article, the paradoxical finding is that a large proportion (35%) of the patients with severe aortic stenosis (AS) have a low-flow state, and thus a low gradient, despite preserved left ventricular ejection fraction. We did not question the reason for the low gradient; this finding was simply a consequence of the low-flow state. We sought, rather, to elucidate why there is a low-flow state in patients with preserved left ventricular ejection fraction. Our findings suggest that paradoxical low flow is a consequence of (1) smaller left ventricular cavity as a result of more pronounced concentric remodeling and the predominance of female gender and (2) intrinsic myocardial dysfunction, as reflected by the lower mid-wall shortening. We also suggested that the markedly higher left ventricular global (valvular and arterial) afterload in paradoxical low-flow patients contributed to the more advanced concentric remodeling and myocardial dysfunction observed in these patients.
For the same degree of AS severity, smaller patients have a lower gradient because they have lower stroke volume. Precisely to avoid this potential selection bias, we used indexed parameters, both for entry in the study and for separation of paradoxical and normal flow groups. As shown in Table 1 of our article,1 the average body surface area of the 2 groups was identical. Hence, body size is unlikely to have affected our results.
In the context of normal left ventricular ejection fraction, it is generally assumed that patients have normal stroke volume, and thus that the recording of a low gradient is incompatible with the presence of severe AS. Patients with paradoxical low flow (eg, aortic valve area 0.8 cm2, mean gradient 29 mm Hg, left ventricular ejection fraction 60%) will generally meet 1 criterion proposed by American College of Cardiology/American Heart Association guidelines for the identification of severe AS (aortic valve area ≤1.0 cm2) but not the other (mean gradient ≥40 mm Hg). This discrepancy may cause some uncertainty and lead clinicians to conclude that AS is not severe and that surgery is not indicated, when in fact these patients are often at a more advanced stage of disease. From our findings, we conclude that (1) normal left ventricular ejection fraction is not synonymous with normal left ventricular flow output in AS patients; (2) it is preferable to rely on indices such as aortic valve area that are less flow-dependent than gradient to assess AS; and (3) beyond the conventional indices of AS severity, valvulo-arterial impedance may be useful for improving risk stratification and management in AS patients, because it better reflects the global afterload imposed on the left ventricle. More specifically, this new index represents the cost in millimeters of mercury for each systemic milliliter of blood indexed for body surface area pumped by the left ventricle during systole.