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Canadian Journal of Cardiology

Sex-Specific Differences in Heart Failure: Pathophysiology, Risk Factors, Management, and Outcomes

      We congratulate Kristen Sullivan et al.
      • Sullivan K.
      • Doumouras B.S.
      • Santema B.T.
      • et al.
      Sex-specific differences in heart failure: pathophysiology, risk factors, management, and outcomes.
      on writing a comprehensive review on “Sex-Specific Differences in Heart Failure: Pathophysiology, Risk Factors, Management, and Outcomes.” The authors should be appreciated for their commendable efforts to cover all the gender differences that exist in heart failure (HF). However, we thought that the addition of a few important points could have enhanced the quality of the article.
      First, there was no mention of the role of genetics in various causes of HF including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy, which show a male predilection. Furthermore, several X-linked disorders, such as Duchenne muscular dystrophy and Danon disease, exhibit varied phenotypes affected by gender, owing to genomic imprinting.
      • Lam C.S.P.
      • Arnott C.
      • Beale A.L.
      • et al.
      Sex differences in heart failure.
      Second, we thought that it was important to mention the role of anthracycline in cardiomyopathy leading to HF, as it is 1 of the most commonly used chemotherapeutic agents in the treatment of breast cancer.
      • Lam C.S.P.
      • Arnott C.
      • Beale A.L.
      • et al.
      Sex differences in heart failure.
      ,
      • De Bellis A.
      • De Angelis G.
      • Fabris E.
      • Cannatà A.
      • Merlo M.
      • Sinagra G.
      Gender-related differences in heart failure: beyond the "one-size-fits-all" paradigm.
      In addition, the prevalent use of alcohol in men is an important risk factor that can lead to HF.
      • De Bellis A.
      • De Angelis G.
      • Fabris E.
      • Cannatà A.
      • Merlo M.
      • Sinagra G.
      Gender-related differences in heart failure: beyond the "one-size-fits-all" paradigm.
      A brief discussion on genetics and these risk factors would have better explained the gender disparity in various determinants of HF.
      Third, the authors should have attempted to shed light on the molecular mechanisms underlying the gender-influenced development of HF. A recent study has described the role of estrogen in the regulation of miRNAs that are responsible for sex-specific differences in cardiovascular diseases. In addition, estrogen receptors prevent atherosclerosis and apoptosis in cardiomyocytes, thus exerting a cardioprotective role in women.
      • De Bellis A.
      • De Angelis G.
      • Fabris E.
      • Cannatà A.
      • Merlo M.
      • Sinagra G.
      Gender-related differences in heart failure: beyond the "one-size-fits-all" paradigm.
      Moreover, in women, mitochondria have better antioxidant properties and provide more resistance against ischemia.
      • De Bellis A.
      • De Angelis G.
      • Fabris E.
      • Cannatà A.
      • Merlo M.
      • Sinagra G.
      Gender-related differences in heart failure: beyond the "one-size-fits-all" paradigm.
      Mentioning these molecular mechanisms would have helped in better understanding the genesis of gender disparities in the development of HF.
      Finally, when comparing the efficacy of various treatment modalities in both genders, we believe that including New York Heart Association functional class would have provided the readers with a better comprehension of the response to different treatment strategies according to the severity of HF.
      • Barsheshet A.
      • Brenyo A.
      • Goldenberg I.
      • Moss A.J.
      Sex-related differences in patients' responses to heart failure therapy.

      Funding Sources

      No funding was provided for this paper.

      Disclosures

      The authors have no conflicts of interest to disclose.

      References

        • Sullivan K.
        • Doumouras B.S.
        • Santema B.T.
        • et al.
        Sex-specific differences in heart failure: pathophysiology, risk factors, management, and outcomes.
        Can J Cardiol. 2021; 37: 560-571
        • Lam C.S.P.
        • Arnott C.
        • Beale A.L.
        • et al.
        Sex differences in heart failure.
        Eur Heart J. 2019; 40 (3859-68c)
        • De Bellis A.
        • De Angelis G.
        • Fabris E.
        • Cannatà A.
        • Merlo M.
        • Sinagra G.
        Gender-related differences in heart failure: beyond the "one-size-fits-all" paradigm.
        Heart Fail Rev. 2020; 25: 245-255
        • Barsheshet A.
        • Brenyo A.
        • Goldenberg I.
        • Moss A.J.
        Sex-related differences in patients' responses to heart failure therapy.
        Nat Rev Cardiol. 2012; 9: 234-242