We thank Dr. Martins for his thoughtful and insightful letter1 regarding our recent study titled “20 years of experience with the Fontan procedure: risk factors for adverse outcomes”.2 We appreciate the opportunity to respond to his important comments regarding the observed sex distribution in our cohort and its potential implications.

We fully acknowledge Dr. Martins’ observation that our study cohort exhibited a male predominance of 67.3% (269/400), a proportion that exceeds that reported in several large international Fontan registries. His letter rightly raises a critical question: whether this imbalance reflects true biological variation or systemic disparities in care. We welcome this discussion as it highlights an increasingly recognized issue in congenital heart disease research – the interplay between biological sex and healthcare equity. Dr. Martins correctly notes that our cohort had a higher male proportion than some registries. However, a review of recent large-scale studies reveals that male predominance is a recurring finding across diverse healthcare systems, though the degree varies among studies:

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  Australia and New Zealand Fontan Registry: 58% male (583/1006).3

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  EuroFontan Registry: 59.1% male (1224/2075).4

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  Mayo Clinic 40-year Follow-up: 61% male (637/1052).5

While our single-center Chinese cohort shows a more pronounced male predominance (67.3%), the direction of the imbalance is consistent with these high-quality, population-based or multi-national studies from Western healthcare systems. This consistency across geographically and socioeconomically diverse settings suggests that the observed sex distribution is unlikely to be explained solely by systematic gender-based inequities in access to care in any one region. Instead, it points toward a complex interplay of factors, possibly including biological differences in the prevalence or severity of certain single-ventricle subtypes, as well as region-specific demographic and referral patterns.

Although sex was not a primary focus of our original analysis, we did include it in our multivariable models. Importantly, male sex was not an independent risk factor for either early mortality (OR 2.3, 95% CI 0.7–8.3, p=0.2) or late Fontan failure (HR 1.4, 95% CI 0.6–3.0, p=0.4). This suggests that within our cohort, the higher proportion of male patients did not translate into worse early or long-term clinical outcomes in our risk-adjusted analysis.

We agree with Dr. Martins that gender-based disparities in diagnosis, referral, and access to surgery are serious concerns that warrant systemic attention. While our retrospective data cannot directly assess these factors, we support ongoing efforts to promote equitable care in congenital heart disease worldwide.

We acknowledge that our study did not include a formal sex-stratified analysis or a discussion of sex-related physiological differences, which Dr. Martins rightly notes could influence Fontan outcomes. This represents a limitation of our work, and we thank him for highlighting this gap. Future studies from our group will endeavor to incorporate sex as a key variable in both analysis and interpretation.

We are grateful to Dr. Martins for initiating this meaningful academic exchange. His letter reinforces the importance of considering sex and equity in outcomes research, and we hope this dialogue encourages further multicenter, prospective studies to better understand these complex issues.