• Aortic Valve Stenosis
• Tomography, Emission-Computed, Single-Photon

Over the last two decades, the differentiation of severe from non-severe aortic valve stenosis with echocardiography has become more complex. The consideration of flow is now frequently essential to evaluate haemodynamic stenosis severity. Low flow can result in low gradient and, thereby, mask severe aortic stenosis. On the other hand, low flow may impede complete opening of the valve and result in overestimation of the severity by aortic valve area (AVA). Since echocardiographic assessment of flow incorporates parameters which are also used to quantify gradient and AVA, measurement errors may lead to major misclassifications of the disease. This has stimulated the search for a method evaluating stenosis severity by morphological criteria independent of haemodynamics. European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines for the management of valvular heart disease 2021 recommend quantification of valve calcification by CT for assessing the severity of aortic stenosis in patients with low gradient. Aortic valve calcification is measured in (arbitrary) Agatston units (AU), and the diagnosis of severe aortic stenosis considered likely with values >2000 in men and >1200 in women. In the two main studies in this field,1 2 areas under the curve (AUCs) from receiver operating characteristic (ROC) for the diagnosis of severe aortic stenosis compared with echocardiography were 0.91 and 0.92 in women and 0.90 and 0.89 in men. Therefore, aortic valve calcification assessed by CT has become a reassuring tool to assess aortic stenosis severity when primary echocardiography alone is inconclusive or doubtful as in cases with assumed or definite low flow and subsequent low gradient. Furthermore, the amount of aortic valve calcification correlates with progression and prognosis of the disease.2 3

The correlation between aortic valve calcification and aortic stenosis severity, as well as sex differences in the degree of calcification in clinical trials, have been studied predominantly in tricuspid aortic valves, or more precisely, irrespective of the definite underlying valve morphology. Bicuspid valve morphology is present in about 16% of patients undergoing valve intervention for severe aortic stenosis4; however, the impact of bicuspid morphology on aortic valve calcification is still under intense investigation. Echocardiographic assessment of bicuspid aortic stenosis can be challenging. Intensive calcifications may impede the recognition of bicuspid morphology, eccentric jets require meticulous search for the appropriate acoustic window to achieve maximal Doppler alignment, and larger left ventricular outflow tract and aortic dimensions may result in complex relations between anatomical and effective AVA further supporting a second diagnostic approach to evaluate stenosis severity.

Ye et al 5 present an important and well-performed retrospective study on 1957 patients including 1344 patients with severe aortic stenosis (AVA ≤1.0 cm² or indexed AVA ≤0.6 cm² plus mean gradient ≥40 mm Hg or peak gradient ≥4 m/s), of whom 328 (17%) had bicuspid morphology. Patients with bicuspid valves were younger (65 vs 81 years), and whereas men with severe aortic stenosis and bicuspid morphology exhibited higher aortic valve calcium score, women showed similar calcium amount compared with individuals with tricuspid valves. These findings remained unchanged after multivariable adjustment for clinical covariates and were similar for aortic valve calcium density (absolute value divided by left ventricular outflow tract area calculated by echocardiography). Best thresholds to differentiate severe from non-severe aortic stenosis with bicuspid morphology were 2916 AU compared with 2246 AU with tricuspid morphology in men, and 1036 AU vs 1069 AU in women. Compared with previous reports, ROC-derived AUCs for the diagnosis of severe aortic stenosis compared with echocardiography in men were lower (bicuspid 0.77; tricuspid 0.81) but similar in women (bicuspid 0.93; tricuspid 0.87).

The study by Ye et al 5 confirms significant differences between women and men in the degree of calcium accumulation in aortic stenosis expanding the results to bicuspid valves. Since not only calcium amount but also calcium density is increased in men compared with women, larger valve size in men does not explain this finding adequately. Recent studies using contrast-enhanced CT for a detailed valve assessment observed more fibrosis and less calcification in severe aortic stenosis in women compared with men6 and improved correlation with echocardiography measuring fibrocalcific volume compared with calcification alone.7 8 Although not yet proven by clinical studies, it seems likely that corresponding findings may also expand to sex differences between tricuspid in bicuspid valves.

The current study showed more calcium deposits in men with bicuspid aortic stenosis compared with those of the same age and with the same degree of stenosis severity and tricuspid morphology. Although the current study is the largest in the field, there are conflicting results with other observations6 and data on patients with non-severe aortic stenosis, especially those with an AVA around the cut-off value of 1.0 cm² and above, are still under-represented. Similarly, there might be a subgroup of young female patients, who may develop severe aortic stenosis with relatively little deposition of calcium6 leading us to the conclusion that more studies are warranted before new guideline-recommended specific thresholds may be indicated. However, the present study reminds us to consider not only age and sex but also valve morphology when using aortic valve calcification in clinical decision-making.

In conclusion, assessment of aortic stenosis may require the application of a second diagnostic method evaluating stenosis severity by morphological criteria independent of haemodynamics in addition to primary echocardiography. The present study by Ye et al 5 confirms a reasonable relationship between the CT-derived degree of valve calcification and stenosis severity irrespective of the underlying valve morphology. Nevertheless, its routine use in the clinical settings may be hampered by the need for a dedicated non-contrast CT. In future, contrast-enhanced CT may be the preferred option, since a CT-based assessment prior to an aortic valve intervention requires contrast enhancement in the majority of patients anyway. The assessment of aortic fibrocalcific volume may have some advantage over the assessment of aortic valve calcification alone particularly in younger female patients. Finally, contrast-enhanced CT additionally allows for the direct morphological assessment of the anatomical AVA, which may be most adequately suited for endorsing or questioning echocardiographic measurements.