Clinical Features,Prognostic Analysis And Pathogenesis Molecular Pathway Exploration Of Left Ventricular Noncompaction

Objective:Left ventricular noncompaction(LVNC)is a rare cardiomyopathy characterized by prominent trabeculae,intratrabecular recesses,and myocardium with both compacted and non-compacted layers.At present,its pathogenesis is still unclear.Previous studies suggested that it may be related to gene mutation or compensation of myocardium to systolic dysfunction or volume overload,but there lacks research on serum markers and pathogenic molecular pathways.Few studies focused on the prognosis of left ventricular noncompaction,and factors related to prognosis of left ventricular noncompaction are still unclear.Also,there is a lack of clinical studies with long-term follow-up in China.The purpose of this study is to summarize the clinical features and explore prognostic related factors of left ventricular noncompaction through a retrospective cohort study,Proteomics techniques were also used to find potential serum markers and molecular pathogenic pathways of left ventricular noncompaction.Methods:This study was a single center,retrospective cohort study,which included inpatients or outpatients in the Department of Cardiology of Peking Union Medical College Hospital from January 1,2008 to December 30,2020.Baseline information,clinical history,laboratory test and imaging examination results of patients were obtained from medical record system.The primary endpoint of this study was cardiovascular death.The secondary endpoint was readmission due to disease progression.Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test.The Cox proportional hazards regression model was used for univariate and multivariate analyses to explore the prognostic risk factors.Serum samples of patients and healthy controls were collected for proteomic analysis.The differentially expressed proteins were identified by bioinformatics analysis,and the potential molecular pathways were explored by GO,KEGG and domain enrichment methods.Results:A total of 70 patients were enrolled in this study.The average age at diagnosis was 46.07 years.Males accounted for 62.9%.During a median follow-up of 75[48-94]months,15 patients died,20 patients re-hospitalized.The mortality rate was 21.4%.Univariate Cox regression analysis showed that male,smoking,BMI,weight loss,NYHA class,Barthel index,neutrophil,D-Dimer,left ventricular ejection fraction(LVEF),left ventricular thrombosis,and right ventricular enlargement were associated with prognosis.Multivariate analysis showed that BMI and right ventricular enlargement were independent prognostic factors for left ventricular noncompaction.Proteomic analysis showed that the expression of immunoglobulin,fibronectin,fibroblast growth factor receptor 1(FGFR1)and vascular endothelial growth factor receptor 3(VEGFR3)were up-regulated in left ventricular noncompaction patients.The main molecular pathways involved are protein phosphorylation pathway,intracellular protein modification pathway and transferase pathway.Most of these pathways are related to inflammation and autoimmune diseases.Conclusion:The clinical manifestations and imaging features of left ventricular noncompaction in our cohort are similar to those reported in previous literatures.Male,smoking,BMI,weight loss,NYHA grade,daily life score,inflammation index,left ventricular ejection fraction(LVEF),left ventricular thrombosis and right ventricular enlargement were prognostic factors for left ventricular noncompaction.Among them,BMI and right ventricular enlargement were independent factors for survival Proteomic studies show that inflammation,immune and fibrosis related pathways may be involved in the development of left ventricular noncompaction.