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Calcific aortic stenosis

Abstract

Calcific aortic stenosis (AS) is the most prevalent heart valve disorder in developed countries. It is characterized by progressive fibro-calcific remodelling and thickening of the aortic valve leaflets that, over years, evolve to cause severe obstruction to cardiac outflow. In developed countries, AS is the third-most frequent cardiovascular disease after coronary artery disease and systemic arterial hypertension, with a prevalence of 0.4% in the general population and 1.7% in the population >65 years old. Congenital abnormality (bicuspid valve) and older age are powerful risk factors for calcific AS. Metabolic syndrome and an elevated plasma level of lipoprotein(a) have also been associated with increased risk of calcific AS. The pathobiology of calcific AS is complex and involves genetic factors, lipoprotein deposition and oxidation, chronic inflammation, osteoblastic transition of cardiac valve interstitial cells and active leaflet calcification. Although no pharmacotherapy has proved to be effective in reducing the progression of AS, promising therapeutic targets include lipoprotein(a), the renin–angiotensin system, receptor activator of NF-κB ligand (RANKL; also known as TNFSF11) and ectonucleotidases. Currently, aortic valve replacement (AVR) remains the only effective treatment for severe AS. The diagnosis and staging of AS are based on the assessment of stenosis severity and left ventricular systolic function by Doppler echocardiography, and the presence of symptoms. The introduction of transcatheter AVR in the past decade has been a transformative therapeutic innovation for patients at high or prohibitive risk for surgical valve replacement, and this new technology might extend to lower-risk patients in the near future.

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Figure 1: The prevalence of AS as a function of age.
Figure 2: Comparison of tricuspid and bicuspid aortic valve structures.
Figure 3: Macroscopic and histopathological appearance of normal and abnormal aortic valves.
Figure 4: Pathogenesis of calcific AS.
Figure 5: Maladaptive remodelling and impaired function of the left ventricle in response to pressure overload from AS.
Figure 6: Patterns of left ventricular remodelling.
Figure 7: Assessment of AS severity by Doppler echocardiography.
Figure 8: Assessment of aortic valve mineralization activity by PET-CT.
Figure 9: Assessment of flow patterns in the aorta by 4D flow cardiac magnetic resonance according to aortic valve phenotype.
Figure 10: Assessment of myocardial fibrosis by cardiac magnetic resonance in patients with AS.
Figure 11: Algorithm for the management of AS.
Figure 12: Different types of surgical aortic valve replacement.
Figure 13: Different types of transcatheter aortic valve replacement.

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Acknowledgements

B.R.L. is supported by the NIH K23 HL116660 and was a Gilead Sciences Research Scholars Program in Cardiovascular Disease Award Recipient. P.P. holds the Canada Research Chair in Valvular Heart Disease and his research programme is funded by the Canadian Institutes of Health Research (Grant numbers FDN-143225, MOP 126072, MOP 114997 and MOP 102737; Ottawa, Ontario, Canada). P.M. is a research scholar from the Fonds de Recherche du Québec-Santé (FRQS) and his research programme is supported by the Canadian Institutes of Health Research (MOP114893, MOP245048 and MOP341860), the Heart and Stroke Foundation of Canada and the Fonds nature et Technologies-Québec.

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Introduction (P.P.); Epidemiology (B.I. and P.P.); Mechanisms/pathophysiology (P.M. and P.P.); Diagnosis, screening and prevention (B.R.L., M.-A.C., P.L., P.M. and P.P.); Management (B.R.L., C.M.O., P.L., P.M. and P.P.); Quality of life (B.R.L., C.M.O. and P.P.); Outlook (B.L. and P.P.); Overview of Primer (P.P.).

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Correspondence to Philippe Pibarot.

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B.R.L. has received research support from and served on the scientific advisory board for Roche Diagnostics. B.I. has received consultant fees from Abbott and Boehringer Ingelheim and speaker's fees from Edwards Lifesciences. P.P. has Core Lab contracts with Edwards Lifesciences, for which he receives no direct compensation. The other authors declare no competing interests.

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Lindman, B., Clavel, MA., Mathieu, P. et al. Calcific aortic stenosis. Nat Rev Dis Primers 2, 16006 (2016). https://doi.org/10.1038/nrdp.2016.6

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