This state-of-the-art review aimed to synthesize evidence from various sex-stratified studies on aortic stenosis (AS), focusing on the difference in clinical presentation, anatomical characteristics, pathophysiology, and management of AS. In comparison to men, women with AS are present at later stages, are older, more symptomatic, frailer, and exhibit higher operative risk [Society of Thoracic Surgeons (STS) score]. Women tend to have smaller aortic valve (AV) areas and left ventricular (LV) outflow tract, leading to lower stroke volumes (SVs) than men and have a higher prevalence of paradoxical, low-flow, low-gradient AS. In women, chronic pressure overload due to AS results in concentric LV remodelling and hypertrophy, characterized by reduced LV cavities, higher filling pressures, lower wall stress, and more diastolic dysfunction. Conversely, men exhibit more dilated eccentric LV remodelling and hypertrophy. AVs in women are less calcified but more fibrotic. Moreover, women are often underdiagnosed, have severity underestimated, and experience delays or receive fewer referrals for AV replacement (AVR). However, women tend to benefit from transcatheter AVR (TAVR) with a long-term survival advantage over men, although the incidence of vascular complications and bleeding events in 30 days after TAVR is higher in women. Surgical AVR (SAVR) in women has high operative risk, is technically demanding and has poorer outcomes with increased mortality at 30 days compared to men. According to the STS score and EuroSCORE, the female sex itself is considered a risk factor for SAVR. Therefore, addressing sex-related disparities in AS and increasing awareness among physicians promises improved diagnosis and treatment, facilitating equitable care and the development of sex-specific personalized medicine.

Department of Cardiology Heart Institute Hospital University Germans Trias i Pujol Barcelona Spain

Department of Cardiology Inselspital Bern University Hospital University of Bern Bern Switzerland

Department of Cardiology Liverpool Heart and Chest Hospital Liverpool UK

Department of Cardiology Normandie Univ UNIROUEN U1096 CHU Rouen Rouen France

Department of General and Interventional Cardiology Angiology Heart and Diabetes Centre Nordrhine Westfalia University Hospital of the Ruhr University Bochum Bad Oeynhausen Germany

Department of Thoracic and Cardiovascular Surgery Heart and Diabetes Center North Rhine Westphalia University Hospital Ruhr University Bochum Bad Oeynhausen Germany

Division of Cardiology and Structural Heart Diseases Medical University of Silesia Katowice Poland

Division of Cardiology Department of Medicine 2 Medical University of Vienna Vienna Austria

Edwards Lifesciences Nyon Switzerland

Edwards Lifesciences Prague Czech Republic

Institute for Pharmacology and Preventive Medicine Cloppenburg Germany

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Steeds RP, Messika-Zeitoun D, Thambyrajah J, et al. IMPULSE: the impact of gender on the presentation and management of aortic stenosis across Europe. Open Heart 2021;8:e001443. 10.1136/openhrt-2020-001443 PubMed DOI PMC

Stewart S, Chan YK, Playford D, et al. Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography. Heart 2022;108:875-81. 10.1136/heartjnl-2021-319697 PubMed DOI

Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005-11. 10.1016/S0140-6736(06)69208-8 PubMed DOI

Iribarren AC, AlBadri A, Wei J, et al. Sex differences in aortic stenosis: Identification of knowledge gaps for sex-specific personalized medicine. Am Heart J Plus 2022;21:100197. 10.1016/j.ahjo.2022.100197 PubMed DOI PMC

Andell P, Li X, Martinsson A, et al. Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study. Heart 2017;103:1696-703. 10.1136/heartjnl-2016-310894 PubMed DOI PMC

Coffey S, Roberts-Thomson R, Brown A, et al. Global epidemiology of valvular heart disease. Nat Rev Cardiol 2021;18:853-64. 10.1038/s41569-021-00570-z PubMed DOI

Cramariuc D, Bahlmann E, Gerdts E. Grading of Aortic Stenosis: Is it More Complicated in Women? Eur Cardiol 2022;17:e21. 10.15420/ecr.2022.13 PubMed DOI PMC

Ancona R, Comenale Pinto S. Epidemiology of aortic valve stenosis (AS) and of aortic valve incompetence (AI): is the prevalence of AS/AI similar in different parts of the world? European Society of Cardiology 2020. Available online: https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-18/epidemiology-of-aortic-valve-stenosis-as-and-of-aortic-valve-incompetence-ai

Aluru JS, Barsouk A, Saginala K, et al. Valvular Heart Disease Epidemiology. Med Sci (Basel) 2022;10:32. 10.3390/medsci10020032 PubMed DOI PMC

Benfari G, Essayagh B, Michelena HI, et al. Severe aortic stenosis: secular trends of incidence and outcomes. Eur Heart J 2024;45:1877-86. 10.1093/eurheartj/ehad887 PubMed DOI

Danielsen R, Aspelund T, Harris TB, et al. The prevalence of aortic stenosis in the elderly in Iceland and predictions for the coming decades: the AGES-Reykjavík study. Int J Cardiol 2014;176:916-22. 10.1016/j.ijcard.2014.08.053 PubMed DOI PMC

Panoulas VF, Francis DP, Ruparelia N, et al. Female-specific survival advantage from transcatheter aortic valve implantation over surgical aortic valve replacement: Meta-analysis of the gender subgroups of randomised controlled trials including 3758 patients. Int J Cardiol 2018;250:66-72. 10.1016/j.ijcard.2017.05.047 PubMed DOI

Bunning CR, Suvarna SK. Native valvular heart disease. Diagnostic Histopathology 2018;24:468-74. 10.1016/j.mpdhp.2018.10.006 DOI

Caponcello MG, Banderas LM, Ferrero C, et al. Gender differences in aortic valve replacement: is surgical aortic valve replacement riskier and transcatheter aortic valve replacement safer in women than in men? J Thorac Dis 2020;12:3737-46. 10.21037/jtd-20-700 PubMed DOI PMC

Fuchs C, Mascherbauer J, Rosenhek R, et al. Gender differences in clinical presentation and surgical outcome of aortic stenosis. Heart 2010;96:539-45. 10.1136/hrt.2009.186650 PubMed DOI

Gaede L, Sitges M, Neil J, et al. European heart health survey 2019. Clin Cardiol 2020;43:1539-46. 10.1002/clc.23478 PubMed DOI PMC

Gaede L, Di Bartolomeo R, van der Kley F, et al. Aortic valve stenosis: what do people know? A heart valve disease awareness survey of over 8,800 people aged 60 or over. EuroIntervention 2016;12:883-9. 10.4244/EIJY16M06_02 PubMed DOI

Hengstenberg C, Thoenes M, Bramlage P, et al. Aortic valve stenosis awareness in Austria-results of a nationwide survey in 1001 subjects. Wien Med Wochenschr 2020;170:141-9. 10.1007/s10354-019-00708-2 PubMed DOI PMC

Bach DS, Radeva JI, Birnbaum HG, et al. Prevalence, referral patterns, testing, and surgery in aortic valve disease: leaving women and elderly patients behind? J Heart Valve Dis 2007;16:362-9. PubMed

Palacios-Fernandez S, Salcedo M, Belinchon-Romero I, et al. Epidemiological and Clinical Features in Very Old Men and Women (≥80 Years) Hospitalized with Aortic Stenosis in Spain, 2016-2019: Results from the Spanish Hospital Discharge Database. J Clin Med 2022;11:5588. 10.3390/jcm11195588 PubMed DOI PMC

Bienjonetti-Boudreau D, Fleury MA, Voisine M, et al. Impact of sex on the management and outcome of aortic stenosis patients. Eur Heart J 2021;42:2683-91. 10.1093/eurheartj/ehab242 PubMed DOI

Goliasch G, Lang IM. Impact of sex on the management and outcome of aortic stenosis patients: a female aortic valve stenosis paradox, and a call for personalized treatments? Eur Heart J 2021;42:2692-4. 10.1093/eurheartj/ehab331 PubMed DOI PMC

Tribouilloy C, Bohbot Y, Rusinaru D, et al. Excess Mortality and Undertreatment of Women With Severe Aortic Stenosis. J Am Heart Assoc 2021;10:e018816. 10.1161/JAHA.120.018816 PubMed DOI PMC

Chaker Z, Badhwar V, Alqahtani F, et al. Sex Differences in the Utilization and Outcomes of Surgical Aortic Valve Replacement for Severe Aortic Stenosis. J Am Heart Assoc 2017;6:e006370. 10.1161/JAHA.117.006370 PubMed DOI PMC

Masiero G, Paradies V, Franzone A, et al. TAVI specific sex consideration. Mini-invasive Surg 2022;6:4.

Stehli J, Johnston R, Duffy SJ, et al. Waiting times of women vs. men undergoing transcatheter aortic valve implantation. Eur Heart J Qual Care Clin Outcomes 2023;9:691-8. 10.1093/ehjqcco/qcac081 PubMed DOI

Szerlip M, Gualano S, Holper E, et al. Sex-Specific Outcomes of Transcatheter Aortic Valve Replacement With the SAPIEN 3 Valve: Insights From the PARTNER II S3 High-Risk and Intermediate-Risk Cohorts. JACC Cardiovasc Interv 2018;11:13-20. 10.1016/j.jcin.2017.09.035 PubMed DOI

Denegri A, Romano M, Petronio AS, et al. Gender Differences after Transcatheter Aortic Valve Replacement (TAVR): Insights from the Italian Clinical Service Project. J Cardiovasc Dev Dis 2021;8:114. 10.3390/jcdd8090114 PubMed DOI PMC

Vlastra W, Chandrasekhar J, García Del Blanco B, et al. Sex Differences in Transfemoral Transcatheter Aortic Valve Replacement. J Am Coll Cardiol 2019;74:2758-67. 10.1016/j.jacc.2019.09.015 PubMed DOI

Itchhaporia D. Transcatheter aortic valve replacement in women. Clin Cardiol 2018;41:228-31. 10.1002/clc.22912 PubMed DOI PMC

Clavel MA, Pibarot P, Messika-Zeitoun D, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol 2014;64:1202-13. 10.1016/j.jacc.2014.05.066 PubMed DOI PMC

Tastet L, Shen M, Capoulade R, et al. Sex Differences in the Progression of Aortic Valve Calcification and Clinical Outcomes: The PROGRESSA Study. JACC Cardiovasc Imaging 2022;15:1349-51. 10.1016/j.jcmg.2022.02.015 PubMed DOI

Peeters FECM, Doris MK, Cartlidge TRG, et al. Sex Differences in Valve-Calcification Activity and Calcification Progression in Aortic Stenosis. JACC Cardiovasc Imaging 2020;13:2045-6. 10.1016/j.jcmg.2020.02.034 PubMed DOI

Summerhill VI, Moschetta D, Orekhov AN, et al. Sex-Specific Features of Calcific Aortic Valve Disease. Int J Mol Sci 2020;21:5620. 10.3390/ijms21165620 PubMed DOI PMC

Patel PP, El Sabbagh A, Johnson PW, et al. Sex Differences in the Impact of Aortic Valve Calcium Score on Mortality After Transcatheter Aortic Valve Replacement. Circ Cardiovasc Imaging 2022;15:e014034. 10.1161/CIRCIMAGING.122.014034 PubMed DOI PMC

Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2022;43:561-632. 10.1093/eurheartj/ehab395 PubMed DOI

Deslandes M, Paquin A, Guzzetti E, et al. Sex-specific correlates of valvular and arterial calcification burden in patients with moderate aortic stenosis. Open Heart 2022;9:e002139. 10.1136/openhrt-2022-002139 PubMed DOI PMC

Naoum C, Blanke P, Dvir D, et al. Clinical Outcomes and Imaging Findings in Women Undergoing TAVR. JACC Cardiovasc Imaging 2016;9:483-93. 10.1016/j.jcmg.2016.02.009 PubMed DOI

Cramariuc D, Rieck AE, Staal EM, et al. Factors influencing left ventricular structure and stress-corrected systolic function in men and women with asymptomatic aortic valve stenosis (a SEAS Substudy). Am J Cardiol 2008;101:510-5. 10.1016/j.amjcard.2007.09.100 PubMed DOI

Ito S, Miranda WR, Nkomo VT, et al. Sex Differences in LV Remodeling and Hemodynamics in Aortic Stenosis: Sex-Specific Criteria for Severe Stenosis? JACC Cardiovasc Imaging 2022;15:1175-89. 10.1016/j.jcmg.2022.02.007 PubMed DOI

Guzzetti E, Poulin A, Annabi MS, et al. Transvalvular Flow, Sex, and Survival After Valve Replacement Surgery in Patients With Severe Aortic Stenosis. J Am Coll Cardiol 2020;75:1897-909. 10.1016/j.jacc.2020.02.065 PubMed DOI

Treibel TA, Kozor R, Fontana M, et al. Sex Dimorphism in the Myocardial Response to Aortic Stenosis. JACC Cardiovasc Imaging 2018;11:962-73. 10.1016/j.jcmg.2017.08.025 PubMed DOI PMC

Elbaz-Greener G, Rahamim E, Abu Ghosh Z, et al. Sex difference and outcome trends following transcatheter aortic valve replacement. Front Cardiovasc Med 2022;9:1013739. 10.3389/fcvm.2022.1013739 PubMed DOI PMC

Carroll JD, Mack MJ, Vemulapalli S, et al. STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement. J Am Coll Cardiol 2020;76:2492-516. 10.1016/j.jacc.2020.09.595 PubMed DOI

Beckmann A, Meyer R, Lewandowski J, et al. German Heart Surgery Report 2017: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery. Thorac Cardiovasc Surg 2018;66:608-21. 10.1055/s-0038-1676131 PubMed DOI

Nguyen V, Willner N, Eltchaninoff H, et al. Trends in aortic valve replacement for aortic stenosis: a French nationwide study. Eur Heart J 2022;43:666-79. 10.1093/eurheartj/ehab773 PubMed DOI

Thaden JJ, Nkomo VT, Suri RM, et al. Sex-related differences in calcific aortic stenosis: correlating clinical and echocardiographic characteristics and computed tomography aortic valve calcium score to excised aortic valve weight. Eur Heart J 2016;37:693-9. 10.1093/eurheartj/ehv560 PubMed DOI PMC

Clavel MA, Dumesnil JG, Capoulade R, et al. Outcome of patients with aortic stenosis, small valve area, and low-flow, low-gradient despite preserved left ventricular ejection fraction. J Am Coll Cardiol 2012;60:1259-67. 10.1016/j.jacc.2011.12.054 PubMed DOI

Stehli J, Zaman S, Stähli BE. Sex discrepancies in pathophysiology, presentation, treatment, and outcomes of severe aortic stenosis. Front Cardiovasc Med 2023;10:1256970. 10.3389/fcvm.2023.1256970 PubMed DOI PMC

O'Brien SM, Shahian DM, Filardo G, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2--isolated valve surgery. Ann Thorac Surg 2009;88:S23-42. 10.1016/j.athoracsur.2009.05.056 PubMed DOI

Williams M, Kodali SK, Hahn RT, et al. Sex-related differences in outcomes after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis: Insights from the PARTNER Trial (Placement of Aortic Transcatheter Valve). J Am Coll Cardiol 2014;63:1522-8. 10.1016/j.jacc.2014.01.036 PubMed DOI

Dagan M, Yeung T, Stehli J, et al. Transcatheter Versus Surgical Aortic Valve Replacement: An Updated Systematic Review and Meta-Analysis With a Focus on Outcomes by Sex. Heart Lung Circ 2021;30:86-99. 10.1016/j.hlc.2020.05.112 PubMed DOI

Tarantini G, Baumgartner H, Frank D, et al. Four-year mortality in women and men after transfemoral transcatheter aortic valve implantation using the SAPIEN 3. Catheter Cardiovasc Interv 2021;97:876-84. 10.1002/ccd.29257 PubMed DOI

Masiero G, Paradies V, Franzone A, et al. Sex-Specific Considerations in Degenerative Aortic Stenosis for Female-Tailored Transfemoral Aortic Valve Implantation Management. J Am Heart Assoc 2022;11:e025944. 10.1161/JAHA.121.025944 PubMed DOI PMC

Bière L, Launay M, Pinaud F, et al. Influence of sex on mortality and perioperative outcomes in patients undergoing TAVR: insights from the FRANCE 2 registry. J Am Coll Cardiol 2015;65:755-7. 10.1016/j.jacc.2014.11.044 PubMed DOI

Sannino A, Szerlip M, Harrington K, et al. Comparison of Baseline Characteristics and Outcomes in Men Versus Women With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation. Am J Cardiol 2018;121:844-9. 10.1016/j.amjcard.2017.12.020 PubMed DOI

Forrest JK, Adams DH, Popma JJ, et al. Transcatheter Aortic Valve Replacement in Women Versus Men (from the US CoreValve Trials). Am J Cardiol 2016;118:396-402. 10.1016/j.amjcard.2016.05.013 PubMed DOI

D'Ascenzo F, Gonella A, Moretti C, et al. Gender differences in patients undergoing TAVI: a multicentre study. EuroIntervention 2013;9:367-72. 10.4244/EIJV9I3A59 PubMed DOI

Chandrasekhar J, Dangas G, Yu J, et al. Sex-Based Differences in Outcomes With Transcatheter Aortic Valve Therapy: TVT Registry From 2011 to 2014. J Am Coll Cardiol 2016;68:2733-44. 10.1016/j.jacc.2016.10.041 PubMed DOI

Humphries KH, Toggweiler S, Rodés-Cabau J, et al. Sex differences in mortality after transcatheter aortic valve replacement for severe aortic stenosis. J Am Coll Cardiol 2012;60:882-6. 10.1016/j.jacc.2012.05.009 PubMed DOI

Wang TY, Gracia E, Callahan S, et al. Gender Disparities in Management and Outcomes Following Transcatheter Aortic Valve Implantation With Newer Generation Transcatheter Valves. Am J Cardiol 2019;123:1489-93. 10.1016/j.amjcard.2019.01.048 PubMed DOI

Saad M, Nairooz R, Pothineni NVK, et al. Long-Term Outcomes With Transcatheter Aortic Valve Replacement in Women Compared With Men: Evidence From a Meta-Analysis. JACC Cardiovasc Interv 2018;11:24-35. 10.1016/j.jcin.2017.08.015 PubMed DOI

Sinning JM, Hammerstingl C, Vasa-Nicotera M, et al. Aortic regurgitation index defines severity of peri-prosthetic regurgitation and predicts outcome in patients after transcatheter aortic valve implantation. J Am Coll Cardiol 2012;59:1134-41. 10.1016/j.jacc.2011.11.048 PubMed DOI

Oterhals K, Hanssen TA, Haaverstad R, et al. Factors associated with poor self-reported health status after aortic valve replacement with or without concomitant bypass surgery. Eur J Cardiothorac Surg 2015;48:283-92. 10.1093/ejcts/ezu425 PubMed DOI

Li SX, Patel NK, Flannery LD, et al. Trends in Utilization of Aortic Valve Replacement for Severe Aortic Stenosis. J Am Coll Cardiol 2022;79:864-77. 10.1016/j.jacc.2021.11.060 PubMed DOI

Sharma T, Krishnan AM, Lahoud R, et al. National Trends in TAVR and SAVR for Patients With Severe Isolated Aortic Stenosis. J Am Coll Cardiol 2022;80:2054-6. 10.1016/j.jacc.2022.08.787 PubMed DOI

Eltchaninoff H, Bonaros N, Prendergast B, et al. Rationale and design of a prospective, randomized, controlled, multicenter study to evaluate the safety and efficacy of transcatheter heart valve replacement in female patients with severe symptomatic aortic stenosis requiring aortic valve intervention (Randomized researcH in womEn all comers wIth Aortic stenosis [RHEIA] trial). Am Heart J 2020;228:27-35. 10.1016/j.ahj.2020.06.016 PubMed DOI

Lindman BR, Fonarow GC, Myers G, et al. Target Aortic Stenosis: A National Initiative to Improve Quality of Care and Outcomes for Patients With Aortic Stenosis. Circ Cardiovasc Qual Outcomes 2023;16:e009712. 10.1161/CIRCOUTCOMES.122.009712 PubMed DOI

Cartlidge TR, Bing R, Kwiecinski J, et al. Contrast-enhanced computed tomography assessment of aortic stenosis. Heart 2021;107:1905-11. 10.1136/heartjnl-2020-318556 PubMed DOI PMC

Powers A, Lavoie N, Le Nezet E, et al. Unique Aspects of Women's Valvular Heart Diseases: Impact for Diagnosis and Treatment. CJC Open 2024;6:503-16. 10.1016/j.cjco.2023.10.017 PubMed DOI PMC