Beyond Sex-Based Differences: Exploring the Complexities of Aortic Stenosis in Women

Aortic Valve Stenosis; Women; Sex Differences; Transcatheter Aortic Valve Replacement; Hypertension, Ventricular Hypertrophy

Sex is an important biological variable in the pathophysiology of cardiovascular disease.¹ , ² In fact, it could determine great differences in manifestation, treatment, and outcomes of several heart disorders. At the level of the aortic valve, there are sex-specific factors related to the pathogenesis of aortic stenosis (AS) that influence hemodynamics changes resulting from pressure overload response, and they should be considered in the management of patients.¹ Despite the fact that sex-based differences in AS exist, they are often not fully recognized and understood, leading to unequal treatment outcomes between males and females.³ , ⁴

This issue of the International Journal of Cardiovascular Sciences presents a comprehensive review of the growing evidence on sex disparities, from the pathogenesis to the treatment of severe degenerative AS, focusing on women.⁵

In this review, entitled “Degenerative aortic stenosis in women: challenges and perspectives,” the authors have pointed out that, in clinical presentation, women are often older and have higher prevalence of hypertension and diastolic dysfunction than men.⁵ Regarding the pathogenic process of degenerative AS, the authors emphasize that, compared to men, women have more concentric ventricular hypertrophy and higher transaortic gradients.⁵ Concentric ventricular remodeling was recognized as a predictor of worse outcome in women, but not in men.⁴ For a given severity degree of AS, women have less valve calcification, measured by computed tomography, with more valvular fibrosis and denser connective tissue than men.⁵ , ⁶ This contrast may have a significant prognostic value since the level of valvular calcification is an independent predictor of disease progression, especially in asymptomatic individuals and could be used to guide referral for intervention.⁶

Also, it is important to note that women may exhibit milder symptoms, and they could often be masked by self-limitation resulting from elderly behavior, which delays the indication for intervention.⁵ , ⁶ In fact, historically, there has been a divergence in the referral of women with severe AS for surgical aortic valve replacement, which is less performed in this sex. This discrepancy could be related to women’s higher post-operative mortality, higher frailty, and elevated risk of patient prosthesis mismatch, due to smaller annular sizes.⁵ - ⁷ However, after the advent of transcatheter aortic valve replacement (TAVR), this disparity has decreased, with an equal representation of women in the utilization of this procedure in the main studies.⁸ , ⁹ Curiously, despite worse pre-procedural female profile and higher rates of bleeding and vascular complications, TAVR has demonstrated improved long-term survival in women, compared to men.¹⁰ Moreover, women have shown improved reverse remodeling of myocardial hypertrophy post-procedure, compared to men.¹¹

This study highlighted the discussion of this critical topic, adding relevant information about innate physiological differences in AS between men and women, but gaps still remain in the current knowledge, and future randomized trials are necessary to elucidate them. Furthermore, the equality in representation of women among TAVR studies does not necessarily translate to equal care and, particularly, optimal timing of valve intervention. Future research should focus on exploring the advantages of using sex-specific guidelines for indicating valve procedures, taking into account the inherent physiological sex variations in AS phenotypes and identifying healthcare factors that may contribute to unequal treatment of women with severe AS.

References

• ¹
  Hahn A, Clavel MA, Mascherbauer J, Meck SL, Asgar AW, Douglas PS. Sex-Related Factors in Valvular Heart Disease. J Am Coll Cardiol. 2022;79(15):1506-18. Doi: 10.1016/j.jacc.2022.08.81.
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• ²
  Shan Y, Pellikka PA. Aortic stenosis in women. Heart. 2020;106(13):970-6. Doi: 10.1136/heartjnl.2019-315407.
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• ³
  Saeed S, Dweck MR, Chambers J. Sex differences in aortic stenosis: from pathophysiology to treatment. Expert Review. Cardiovasc Ther. 2020;18(2):65-76. Doi: 10.1080/14779072.2020.1732209.
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• ⁴
  Capoulade N, Clavel MA, Le Ven F, Dahou A, Thebault C, Taste L, et al. Impact of left ventricular remodelling patterns on outcomes in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging. 2017;18(12):1378-87. Doi: 10.1093./ehjci/jew288.
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• ⁵
  Oliveira GMM, Ferreira MCM, Nercolini DC, de Oliveira MV, dos Santos MA, et al. Degenerative Aortic Stenosis in Women: Challenges and Perspectives. Int J Cardiovasc Sci. 2023;36:e20210261. Doi: 10.36660/ijcs.20210261.
  » https://doi.org/10.36660/ijcs.20210261.
• ⁶
  Goel H, Kumar A, Gang N, Mills JD. Men are from mars, women are from venus: Factors responsible for gender differences in outcomes after surgical and trans-catheter aortic valve replacement. Trends Cardiovasc Med. 2021;31(1):34-46. Doi: 10.1016/i-tcm.2019.11.010.
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• ⁷
  Chaker Z, Badhwar V, Alqahtani F, Aljohani S, Zack CJ, Holmes DR, et al. Sex differences in the utilization and outcomes of surgical aortic valve replacement for severe aortic stenosis. J Am Heart Assoc. 2017;6(9):e006370. Doi: 10.1161/JAMA.117.006370.
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• ⁸
  Pacheco C, Henri C, Forcillo J, Asgar AW. Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis in Women: Clinical Characteristics and Outcomes. Can J cardiol. 2018;34(4):422-8. Doi: 10.1016/j.cjca.2017.10.026.
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• ⁹
  Saad M, Nairooz R, Pathieneni NVK, Almomani A, Kovelamude S, Sarclar P, 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(1):24-35.
• ¹⁰
  Williams M, Kodali SK, Hahn RT, Humphries KH. Sex-Related Differences in Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis. J Am Coll Cardiol. 2014;63(15):1522-8. Doi: 10.1016/j.jacc.2014.01.036.
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• ¹¹
  Petrov G, Regitz-Krabatsch T, Dunkel A, Dandel M, et al. Regression of Myocardial Hypertrophy After Aortic Valve Replacement. Circulation. 2010;122(11):S23-8. Doi: 10.1161/CIRCULATIONAHA.109.9277.
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• Editorial referring to the article: Degenerative Aortic Stenosis in Women: Challenges and Perspectives

Publication Dates

• Publication in this collection
  17 July 2023
• Date of issue
  2023