Single ventricle (SV) deficits are rare congenital heart defects characterized by either one severely underdeveloped ventricle, or the absence of the ventricular septum, resulting in a broad range of cardiac structural abnormalities [1, 2]. This life-threatening congenital heart defect necessitates prompt intervention, commonly through the Fontan operation [2, 3, 4]. This Fontan procedure, which may be executed in either one or multiple stages as a total cavopulmonary connection, provides palliation and treatment, achieving satisfactory long-term survival for SV patients [3, 4]. However, it carries risks of both cardiac and non-cardiac complications that could lead to Fontan failure, primarily due to decreased cardiac output and persistent elevated systemic venous pressure from the absence of a sub-pulmonary ventricle [5, 6]. Consequently, extensive research is underway to identify risk factors and improve Fontan techniques, aiming to enhance patient outcomes.

Morphological variations SV deficits can be categorized as left, right, or indeterminate. It is hypothesized that Fontan patients with a dominant right ventricle (RV) experience worse outcomes compared to those with a dominant left ventricle (LV), potentially due to differences in anatomy, embryological origin, and affiliated atrioventricular valves [7, 8]. Nevertheless, the impact of RV dominance on Fontan procedure outcomes continues to be a controversial issue [9, 10, 11], likely influenced by the significant heterogeneity observed in Fontan patients.

Despite evidence from previous studies suggesting that RV dominance in Fontan circulation, particularly among patients with hypoplastic left heart syndrome (HLHS), leads to poorer outcomes compared to those with LV-dominance [12, 13], the reasons for this discrepancy are multifaceted. It’s speculated that the theoretical disadvantages of RV dominance are compounded by factors such as increased aortic stiffness and higher systemic afterload, outcomes often associated with Norwood surgery, further disadvantaging RV dominant systems [14, 15]. The connection between ventricular dominance and patient outcomes in non-HLHS Fontan circulation, however, remains unclear and contentious.

This ambiguity highlights the need for a nuanced understanding of how ventricular dominance influences long-term health and recovery in Fontan patients. Considering this complexity, we developed a propensity score matching (PSM) system aimed at reducing patient heterogeneity. This method enabled us to conduct a direct comparison of long-term outcomes between RV and LV dominance in Fontan patients, specifically excluding those with HLHS.

The association between RV-dominance and poorer long-term outcomes in Fontan circulation is a subject of ongoing debate. Our study employed PSM to balance patient characteristics between pre- and intra-Fontan status, focusing on those with non-HLHS, to compare outcomes between RV and LV dominance. Our findings revealed that: (1) The cumulative incidence of AVVR was similar between the two groups in both the prematched cohort and the matched cohort. (2) Dominant ventricular morphology did not significantly impact the likelihood of long-term freedom from death or transplantation and Fontan failure in either the prematched or matched cohorts. These results suggest that the ventricular morphology, whether RV or LV dominance, does not decisively influence the long-term success of Fontan circulation in the non-HLHS patient population.

Anatomical and embryological distinctions between the RV and LV, along with differences in AVV, suggest the RV might be more susceptible to pressure-overload when it assumes responsibility for systemic circulation, potentially, leading to or accelerating the occurrence and progression of AVVR [16]. Indeed, previous studies [17] revealed a higher rate of AAVR deterioration and progression AVVR in patients with RV dominance compared to those with LV dominance in Fontan circulation. Of note, instances of moderate or greater AVVR at the time of Fontan operations and subsequent AVV repair or replacement were more common in the dominant RV group. However, specific details regarding AVV morphology in these comparisons remained unclear.

Contrary to these observations, our study found no significant difference in the cumulative incidence of moderate or greater AVVR between the prematched RV and LV dominant groups. Further, after matching patients for similar clinical AVV status, we observed equivalent rates of AVVR across RV and LV dominant Fontan patients. This echoes findings from a recent retrospective study of 174 Fontan patients with atrioventricular septal defect, showing no significant difference of moderate or greater AVVR between the two groups [18]. This suggests that AVV morphology and anatomy may play a more critical role in AVVR development than ventricular dominance itself.

Moreover, in our matched cohorts, the 10-year cumulative incidence of moderate or greater AVVR was closely matched between the RV and LV dominant groups, at 11% $\pm$ 5% and 15% $\pm$ 6%, respectively, which was consistent with previous studies [19]. For instance, King et al. [17] reported a 10% incidence of moderate or greater AVVR 10 years after Fontan surgery in a large retrospective study involving 1703 patients. These outcomes collectively indicate that while ventricular dominance may not significantly influence AVVR progression, the specific morphological and anatomical features of the AVV are crucial determinants of AVVR development in Fontan patients.

Our study demonstrates that the long-term outcomes following Fontan operation, specifically freedom from death or transplantation and freedom from Fontan failure, do not significantly differ between patients who are RV-dominant and LV-dominant. In the matched groups, the 10-year freedom from death or transplantation was 84% $\pm$ 7% in the matched RV-dominant group, similar to 81% $\pm$ 7% in the matched LV-dominant group (p $>$ 0.05). Additionally, the 10-year freedom from Fontan failure was 78% $\pm$ 8% in the matched RV-dominant group versus 75% $\pm$ 8% in the matched LV-dominant group (p $>$ 0.05). Furthermore, RV dominance was not identified as an independent risk factor for Fontan failure in our multivariate analysis.

This finding aligns with previous studies that presents varied and often contradictory evidence on the impact of dominant ventricular morphology on long-term outcomes in Fontan circulation [11, 20, 21, 22, 23, 24, 25]. For example, Hosein et al. [26] retrospectively analyzed 406 Fontan patients (60% HLHS in the RV-dominant group) during the mean follow-up of 6.1 years, showing that ventricular morphology did not adversely influence short-term or long-term outcomes of Fontan patients. The freedom from death or transplantation at 5 years and 10 years after the Fontan operation was 90% and 86%, respectively, which was consistent with our findings [26]. These consistencies across studies suggest that despite the theoretical implications of ventricular morphology on post-Fontan prognosis, the actual influence may be minimal, underscoring the need for a nuanced understanding of individual patient characteristics and the multifactorial nature of outcomes following Fontan surgery.

In contrast, Moon et al. [11] conducted a retrospective study of 1162 patients with a direct focus on ventricular morphology, with 71% of these patients classified as RV-dominant with HLHS. With a mean follow-up of 8.3 years, they concluded that RV dominance impaired long-term outcomes when compared to the LV-dominant group, potentially due to AVVR deterioration and impaired ventricle function [11]. Notably, they reported a 10-year transplantation-free survival rate of 90% in the RV-dominant group, significantly lower than 92% in the LV-dominant group (p 0.05), which differed from our findings [11].

Several factors may account for these contrasting results. First, the inherent heterogeneity among Fontan patients, who present with a wide variety of congenital cardiac structural abnormalities, may contribute to these discrepancies. Indeed, many previous studies showed an imbalance in baseline anatomic characteristics between the two groups [11, 18]. Our application of PSM aimed to reduce the selection bias, resulting in outcomes that were similar between groups. This suggests the possibility that inherent cardiac structural abnormalities, rather than RV-dominant morphology influence long-term outcomes. Secondly, the incidence of moderate or greater AVVR, a factor known to affect outcomes due to its contribution to volume overloading, ventricular dilation, and increased central venous pressure, was maintained between groups in our study [5]. This similarity in AVVR progression supports the idea that ventricular dominance may not be the primary determinant of outcomes. Thirdly, follow-up durations in our study were slightly shorter than in Moon’s study, with 8.0 years for RV dominance and 6.5 years for LV dominance in our study vs. 8.3 years in Moon’s study [11]. It’s possible that the systemic circulation supported by the dominant RV could remain in a compensatory state within this timeframe, leading to outcomes that did not significantly differ from those of the LV-dominant group. Lastly, our exclusion of HLHS patients, who are generally at higher risk for adverse outcomes, may have minimized the perceived disadvantages of the RV-dominant group, contributing to our findings of similar outcomes [12]. The exclusion criteria perhaps weakened the disadvantage of the RV-dominant group, partially contributing to the finial similar results. Regardless, despite differing perspectives in the literature, our research suggests that the long-term prognosis for dominant RV and LV in non-HLHS Fontan patients may be similar, at least within the duration of our follow-up period.

There were several limitations in our study. First, this is a single-center study with a retrospective design, which may limit the applicability of the findings to broader populations. Secondly, the relatively small sample size of Fontan patients both before and after PSM could diminish the statistical power of our results. Finally, although cardiac magnetic resonance imaging remains the gold standard for determining functional ventricular dominance through quantification of cardiac output and stroke volume, it was not typically utilized before Fontan operations in our hospital due to the high cost and long waiting periods for appointments. Consequently, ventricular dominance was assessed using echocardiography, a method that may not provide an ideal assessment for all patients. This potentially led to the exclusion of some patients categorized as having indeterminate or biventricular morphology from this analysis.

The RV dominance does not seem to adversely influence the long-term outcomes in non-HLHS Fontan circulation. The likelihood of experiencing moderate or greater AVVR, transplantation-free survival, and avoiding Fontan failure were similar between RV and LV dominant groups within in the same pre- and intra-Fontan conditions.

SV, single ventricle; RV, right ventricle; LV, left ventricle; HLHS, hypoplastic left heart syndrome; PSM, propensity score matching; AVVR, atrioventricular valve regurgitation; AVV, atrioventricular valve.

Data are available from the corresponding author upon reasonable request.

HYY and JMC designed the research. HW, JRM, and LJH performed the research. TT, WX, MT, ZCT, and YL were in charge of data collection. XL, XBL, HYY, and JMC provided help and advice on research. HW and JRM analyzed the data and wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Ethical approval was obtained from the Guangdong Provincial People’s Hospital Ethics Committee on 17th September 2019 (No. GDREC2019338H(R2)). The individual informed consent was waived due to the retrospective design of the study.

We appreciated the helpful comments of each member from Zhuang’s and Chen’s group.

This study was supported by the project of National Key R&D Program of China (No. 2022YFC2407406), Stability Support for Innovation Capacity Building of Research institutions in Guangdong Province in 2022 (KD022022015) and Science and Technology Fundation of Guangzhou Health (No. 2023A031004).

The authors declare no conflict of interest.