Assessment of Right Ventricular Endocardial Fibroelastosis in Fetuses with Critical Pulmonary Stenosis and Pulmonary Atresia with Intact Ventricular Septum

Background Systematic assessment of right ventricular (RV) endocardial fibroelastosis (EFE) in the fetus with critical pulmonary stenosis and pulmonary atresia with intact ventricular septum (CPS/PA-IVS) has not been reported. The implications of RV EFE for circulatory outcomes with or without fetal cardiac intervention (FCI) have also not been demonstrated. Methods The fetal echocardiographic data from July 2018 to January 2021 in a single-center institution were collected. Three reviewers independently graded EFE according to the presence and extent of endocardial echogenicity. The associations among EFE severity, anatomic variables, and postnatal outcomes were analyzed. Results 81 cases with RV EFE were identified. By consensus, EFE severity was assessed as grade 1 (“mild”; n=66, 81.48%), grade 2 (“moderate”; n=11, 13.58%), and grade 3 (“severe”; n=4, 4.94%). RV sphericity values were greater in grade 2 and 3 EFE groups compared to the grade 1 EFE group, implying more severe noncompliance and worse diastolic function. 10/81(12.35%) fetuses underwent FCI. At the latest available follow-up, 59/81 (72.84%) patients had achieved biventricular circulation. Furthermore, 9/59 (15.25%)—four with grade 1 EFE, three with grade 2, and two with grade 3—had undergone FCI, whereas the other 50/59 (84.75%)—who all had grade 1 EFE—had not. Conclusions For the first time in CPS/PA-IVS, RV EFE was graded and the potential of FCI to improve the prognosis of non-mild RV EFE patients was revealed. Non-mild RV EFE was suggested to be a putative indicator of FCI. ![Figure][1] ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial No clinical trials or any other prospective studies. ### Funding Statement This work was supported by the National Natural Science Foundation of China (82271725 and 81970249), and Technology Benefit People Demonstration and Guidance Special Project (23-2-8-smjk-10-nsh). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by Ethics Committee of Medical College of Qingdao University (QDU-HEC-2022142). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data referred to in the manuscript are available from the corresponding author upon reasonable request. * AV : aortic valve BiV : biventricle CPS : critical pulmonary stenosis EFE : endocardial fibroelastosis EndMT : endothelial-to-mesenchymal transition FCI : fetal cardiac intervention FPV : fetal pulmonary valvuloplasty HLHS : hypoplastic left heart syndrome LV : left ventricle LVOT : left ventricular outflow tract MV : mitral valve PA-IVS : pulmonary atresia with intact ventricular septum PBPV : percutaneous balloon pulmonary valvuloplasty PDA : patent ductus arterios PV : pulmonary valve RV : right ventricle RVOT : right ventricular outflow tract TV : tricuspid valve. [1]: pending:yes