Sex-Based Differences in Heart Transplantation: Key Points

DeFilippis EM, Nikolova A, Holzhauser L, Khush KK.
Understanding and Investigating Sex-Based Differences in Heart Transplantation: A Call to Action. JACC Heart Fail 2023;11:1181-1188.

The following are key points to remember about sex-based differences in heart transplantation:

  1. Women are less likely to be referred to an advanced heart failure specialist for evaluation for advanced therapies, with women only representing 21% of left ventricular assist device implantations and 25% of those on the heart transplant waitlist, despite accounting for 54% of deaths caused by heart failure.
  2. Health care disparities arising from implicit bias among health care providers may lead to fewer women eligible for heart transplantation and this bias may also extend to racial differences. Frailty is more commonly observed in women with heart failure than men and objective measures of frailty should be used to prevent perception bias when being assessed.
  3. Women have higher waitlist mortality; however, the incidence of waitlist removal for death or delisting for women was lower in the 2018 six-tiered allocation system compared with the previous three-tiered heart allocation system. Disparities still exist with reports of Status 1 women candidates experiencing a lower rate of heart transplant compared with men (adjusted hazard ratio [aHR], 0.75; 95% confidence interval [CI], 0.62-0.88) and higher rate of delisting for death or clinical deterioration (aHR, 1.48; 95% CI, 1.05-2.09).
  4. Misconceptions related to sex-mismatched heart transplant outcomes negatively impact organ matching and result in unnecessary waste of donor organs. Prior reported negative outcomes may have been associated with poor size matching, with undersized hearts resulting in a 20-30% increase in mortality and higher risk of requiring treatment for acute rejection. Predicted heart mass (PHM) is the current standard metric for size matching. International Society for Heart and Lung Transplantation (ISHLT) guidelines on donor heart selection specify that female donor to male recipient allocation may be done safely when adequate donor/recipient weight ratio and/or PHM is ensured.
  5. Allosensitization is more common in women as they are more likely to experience sensitization from prior pregnancy, which may result in decreased referrals/listing, prolonged waitlist time, and increase in waitlist mortality. Women with preoperative sensitization have been reported to be more likely to experience acute rejection, antibody mediated rejection, and moderate–severe rejection post–heart transplantation. Outcomes related to the efficacy of desensitization have been conflicting and the ability to compare data across centers would be improved by standardization of human leukocyte antigen laboratory antibody identification and quantitation.
  6. Women may be more likely to benefit from induction immunosuppression than men given higher rates of rejection. Induction with T-cell depleting agents was associated with a survival benefit in women compared with no induction; this benefit was not found with interleukin-2 receptor antagonists or in men. Further studies are warranted to determine optimal immunosuppression strategies and impact of sex differences post–heart transplantation.
  7. Male donor sex has been identified in one study as an early independent predictor of cardiac allograft vasculopathy. Male heart transplant recipients tend to be older and have a higher prevalence of comorbidities such as diabetes, dyslipidemia, hypertension, and history of tobacco use.
  8. Women may be less likely to experience malignancy (25.7 vs. 44.8 per 1,000 person-years; relative risk [RR], 0.68) after heart transplantation and have lower cancer mortality rates (94 vs. 129.6 per 1,000 person-years; RR, 0.76) compared to men.
  9. Women have reported being more satisfied with overall social and emotional support than men post–heart transplant and are more likely to comply with recommendations for sun protection, tobacco cessation, and alcohol consumption.
  10. Pregnancy is not recommended within the first year after heart transplantation and women of childbearing potential should be counseled on effective contraceptive options. Mycophenolate products are teratogenic and should be discontinued at least 6 weeks before conception. If pregnancy is desired, shared decision making with the patient combined with extensive preconception risk counseling with a multidisciplinary team is essential.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant

Keywords: Heart Failure, Heart Transplantation, Immunosuppression, Pregnancy, Sex Characteristics

< Back to Listings