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There are no recommendations for patients with moderate aortic stenosis and left ventricular dysfunction, despite the high associated morbidity and mortality. There is also some evidence that these patients may benefit from early aortic valve intervention. It is recognised that aortic stenosis not only affects the valve but also has a complex myocardial response. This review discusses the natural history of moderate aortic stenosis along with the role of multimodality imaging in risk stratification in these patients.<\/jats:p>","DOI":"10.15420\/icr.2021.04","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T16:34:29Z","timestamp":1622565269000},"source":"Crossref","is-referenced-by-count":24,"title":["Moderate Aortic Stenosis: What is it and When Should We Intervene?"],"prefix":"10.15420","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7688-4936","authenticated-orcid":false,"given":"Sveeta","family":"Badiani","sequence":"first","affiliation":[{"name":"Heart Valve Clinic and Echocardiography Laboratory, Barts Heart Centre, St Bartholomew\u2019s Hospital, London, UK; William Harvey Research Institute, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-5366","authenticated-orcid":false,"given":"Sanjeev","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Heart Valve Clinic and Echocardiography Laboratory, Barts Heart Centre, St Bartholomew\u2019s Hospital, London, UK; William Harvey Research Institute, Queen Mary University of London, UK; Institute of Cardiovascular Sciences, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5333-1194","authenticated-orcid":false,"given":"Nikoo","family":"Aziminia","sequence":"additional","affiliation":[{"name":"Heart Valve Clinic and Echocardiography Laboratory, Barts Heart Centre, St Bartholomew\u2019s Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-7414","authenticated-orcid":false,"given":"Thomas A","family":"Treibel","sequence":"additional","affiliation":[{"name":"Heart Valve Clinic and Echocardiography Laboratory, Barts Heart Centre, St Bartholomew\u2019s Hospital, London, UK; Institute of Cardiovascular Sciences, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1958-6606","authenticated-orcid":false,"given":"Guy","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Heart Valve Clinic and Echocardiography Laboratory, Barts Heart Centre, St Bartholomew\u2019s Hospital, London, UK; William Harvey Research Institute, Queen Mary University of London, UK; Institute of Cardiovascular Sciences, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6096","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Bohbot Y, Rusinaru D, Delpierre Q, et al. 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Circulation 2002;106:809\u201313. https:\/\/doi.org\/10.1161\/01.cir.0000025611.21140.34; PMID:\u00a012176952.","DOI":"10.1161\/01.cir.0000025611.21140.34"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Messika- Zeitoun D, Aubry MC, Detaint D, et al. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation 2004;110:356\u201362. https:\/\/doi.org\/10.1161\/01.CIR.0000135469.82545.D0; PMID:\u00a015249504.","DOI":"10.1161\/01.cir.0000135469.82545.d0"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Dweck MR, Jenkins WS, Vesey AT, et al. 18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circ Cardiovasc Imaging 2014;7:371\u201378. https:\/\/doi.org\/10.1161\/CIRCIMAGING.113.001508; PMID:\u00a024508669.","DOI":"10.1161\/circimaging.113.001508"},{"key":"ref65","unstructured":"Jenkins WS, Vesey AT, Shah AS, et al. 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Circ Cardiovasc Imaging 2018;11:e007451. https:\/\/doi.org\/10.1161\/CIRCIMAGING.117.007451; PMID:\u00a029914867.","DOI":"10.1161\/circimaging.117.007451"},{"key":"ref73","doi-asserted-by":"crossref","unstructured":"Musa TA, Treibel TA, Vassiliou VS, et al. Myocardial scar and mortality in severe aortic stenosis. Circulation 2018;138:1935\u201347. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.117.032839; PMID:\u00a030002099.","DOI":"10.1161\/CIRCULATIONAHA.117.032839"},{"key":"ref74","unstructured":"Everett RJ, Treibel TA, Fukui M, et al. Extracellular myocardial volume in patients with aortic stenosis. J Am Coll Cardiol 2020;75:304\u201316. https:\/\/doi.org\/10.1016\/j.jacc.2019.11.032; PMID:\u00a031976869."},{"key":"ref75","doi-asserted-by":"crossref","unstructured":"Treibel TA, Kozor R, Schofield R, et al. Reverse myocardial remodeling following valve replacement in patients with aortic stenosis. J Am Coll Cardiol 2018;71:860\u201371. https:\/\/doi.org\/10.1016\/j.jacc.2017.12.035; PMID:\u00a029471937.","DOI":"10.1016\/j.jacc.2017.12.035"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"Bing R, Everett RJ, Tuck C, et al. Rationale and design of the randomised, controlled early valve replacement guided by biomarkers of left ventricular decompensation in asymptomatic patients with severe aortic stenosis (EVOLVED) trial. Am Heart J 2019;212:91\u2013100. https:\/\/doi.org\/10.1016\/j.ahj.2019.02.018; PMID:\u00a030978556.","DOI":"10.1016\/j.ahj.2019.02.018"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"Cavalcante JL, Rijal S, Abdelkarim I, et al. Cardiac amyloidosis is prevalent in older patients with aortic stenosis and carries worse prognosis. J Cardiovasc Magn Reson 2017;19:98 https:\/\/doi.org\/10.1186\/s12968-017-0415-x; PMID:\u00a029212513.","DOI":"10.1186\/s12968-017-0415-x"},{"key":"ref78","unstructured":"Nitsche C, Scully PR, Patel KR, et al. Prevalence and outcomes of concomitant aortic stenosis and cardiac amyloidosis. J Am Coll Cardiol 2021;77:128\u201339. https:\/\/doi.org\/10.1016\/j.jacc.2020.11.006; PMID:\u00a033181246."},{"key":"ref79","unstructured":"Chan DCS, Singh A, Greenwood JP, et al. Effect of the 2017 European guidelines on reclassification of severe aortic stenosis and its influence on management decisions for initially asymptomatic aortic stenosis. 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