Despite a nearly equal distribution of heart failure between men and women, multiple studies have demonstrated decreased utilization of and worse outcomes after Left ventricular assist device (LVAD) implantation among women.1,2 The current study by Lamba et al.3 furthers this finding, raising important questions about the role of pre- and postright ventricular failure in women undergoing LVAD implantation. Additionally, this study highlights the fundamental importance and a critical call to action with respect to equity in gender enrollment during clinical trials and retrospective studies.

Using Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data, the authors generate two propensity matched models that reveal a significant difference between men and women with regard to survival after LVAD implantation, which may be accounted for by differences in the stage in their disease course and degree of right heart failure at the time that men and women undergo LVAD implantation. In the first model, two groups of men and women over 50 years old were matched based on severity of heart failure (INTERMACS classes 1 and 2), comorbidities, body surface area, as well use of LVAD as bridge to transplant or destination therapy. Based on the outcome of this propensity model, which revealed higher rates of pre- and post-LVAD right ventricular failure, worse 1 year mortality and lower rates of transplantation among women, the authors then generated a second propensity matched model in which two groups of men and women were matched using all the characteristics of the first model in addition to variables characterizing the degree of right heart failure as well as Left ventricular end diastolic diameter (LVEDD) at the time of LVAD placement. The results of this model revealed that when matched for degree of right heart failure and LVEDD at the time of LVAD implantation, similar outcomes were seen between men and women with regard to 1 year mortality, need for postoperative right heart mechanical support, and heart transplantation.

The exact mechanisms that underlie this discrepancy between men and women with regard to outcomes after LVAD implantation are not elucidated, but this article highlights areas for further investigation. Can it be explained by the discrepancies in access to LVAD therapy and delayed consideration for advanced therapies? Or is there a physiologic characteristic that predisposes women to worsened right heart failure and thus worse survival after LVAD implantation? In this study, when patients were matched for LVEDD and preoperative right heart failure, outcomes were equivalent. A potential variable that the authors highlight is the role that left ventricular size may play in the development of right heart failure post-LVAD implantation, as smaller left ventricular size has been associated with worse outcomes after LVAD implantation, potentially due to adverse interventricular septal leftward shifts which may in part explain the increased rates of right heart failure seen in women with smaller ventricular diameters.4,5 Another recent study by Molina et al.6 reveals equivalent outcomes after LVAD implantation when comparing large and small Body surface area (BSA) patients but makes note of the limited number of patients with small LVEDDs in their study and that the role of LV size and its interplay with overall body size and LVAD outcomes warrants further study. Perhaps given womens’ on average smaller body size, women require a greater degree of left ventricular dilation relative to their BSA to benefit from LVAD and thus are presenting at later, more advanced stages of heart failure. Finally, an important limitation of the article is that none of the patients included in this study underwent implantation of the only current commercially available continuous flow LVAD, the Heartmate III. Further study is warranted to elucidate if the findings hold true with the current device.

While Lamba et al.3 should be applauded for highlighting and subsequently investigating the fact that an increased degree of right heart failure is observed in women undergoing LVAD implantation when compared with their male counterparts, this finding is not entirely unexpected given the degree of gender misrepresentation in heart failure clinical trials for more than 20 years. For example, Whitelaw et al.7 performed a review of more than 300 randomized control trials within the heart failure space from 2000 to 2019. What was identified is that nearly 75% of the heart failure trials under-enrolled women, as benchmarked by a threshold of less than 32% enrolled women subjects. These statistics are shocking. With nearly equal numbers of men and women suffering from heart failure, none of us should be surprised that we are now uncovering gender-specific differences related to outcomes in this population of people.

This article is a call to action. We as a heart failure and transplant community cannot continue to accept worse outcomes for women in our field as a result of misrepresentation in clinical trials and retrospective research. We must do better to not only study the outcomes of women with heart failure such as what Lamba et al.3 have done in this article, but also to bolster the enrollment of women in trials via multisector collaboration across academic institutions and industry.

1. Shetty NS, Parcha V, Abdelmessih P, et al.: Sex-associated differences in the clinical outcomes of left ventricular assist device recipients: insights from interagency registry for mechanically assisted circulatory support. Circ Heart Fail. 16: e010189, 2023. 2. Gruen J, Caraballo C, Miller PE, et al.: Sex differences in patients receiving left ventricular assist devices for end-stage heart failure. JACC Heart Fail. 8: 770–779, 2020. 3. Lamba HK, Kherallah R, Nair AP, et al.: Sex disparities in left ventricular assist device implantation: delayed presentation and worse right heart failure. ASAIO J. 70: 469–476, 2024. 4. Anne Dual S, Nayak A, Hu Y, Schmid Daners M, Morris AA, Cowger J: Does size matter for female continuous-flow LVAD recipients? A translational approach to a decade long question. ASAIO J. 68: 21–27, 2022. 5. Molina E, Jain A, Ahmed S, et al.: The impact of left ventricular size on outcomes after centrifugal-flow left ventricular assist device implantation. Eur J Cardiothorac Surg. 62: ezab480, 2022. 6. Molina EJ, Cowger J, Lee S, et al.: Outcomes in smaller body size adults after HeartMate 3 left ventricular assist device implantation. Ann Thorac Surg. 114: 2262–2269, 2022. 7. Whitelaw S, Sullivan K, Eliya Y, Alruwayeh M, Thabane L, Yancy CW, Mehran R, Mamas MA, Van Spall HGC. Trial characteristics associated with under-enrolment of females in randomized controlled trials of heart failure with reduced ejection fraction: a systematic review. Eur J Heart Fail. 23: 15–24, 2021. doi: 10.1002/ejhf.2034. Epub 2020 Nov 16. PMID: 33118664.