| Objective(s):Metabolomics analysis was used to identify myocardial fibrosis plasma metabolites in patients with HCM,and cardiac nuclear magnetic T1 mapping technique was used to quantitatively evaluate myocardial fibrosis,so as to explore the value of both in definite diagnosis and prognosis assessment of hypertrophic cardiomyopathy.Methods: 30 patients with HCM(experimental group)and 30 hypertensive patients with normal ventricular wall thickness(control group)admitted to the First Affiliated Hospital of Kunming Medical University from June 2021 to October 2022 were included.Plasma,clinical data and CMR data of all patients in the experimental group and control group were collected.Including Late gadolinium enhancement(LGE)and T1 mapping sequence,image analysis and processing of post-processing workstation,it is concluded that the heart related parameters,The American Heart Association(AHA)has published the nomenclature and segmentation(the 17 segments cardiac segmentation model)of the left ventricular myocardium and The left ventricular myocardium was segmented according to this method.The Native T1,post T1 and Extracellular volume fraction(ECV)of each segment were measured.All patients were prospectively followed up.To collect blood samples based on Ultra Performance Liquid Chromatography(UHPLC)and LC-MS/MS technology for metabonomics analysis of samples,multivariate statistical analysis was carried out on the patients with plasma metabolites,Including the principal component analysis(PCA),Partial Least Squares Discrimination Analysis(PLS-DA),etc.,revealing the different groups of different metabolic patterns.Using Hierarchical Clustering Alg(HCA)and correlation analysis of metabolites,reveal the relationship between samples and metabolites and metabolites and major metabolic pathways.The metabolites and CMR parameters were analyzed by COX univariate and multivariate regression to explore their relationship with the occurrence of HCM endpoint events.Finally,Kaplan-Meier survival analysis was combined to explore the prognostic value of HCM endpoint event influencing factors for HCM.Results: 30 HCM patients were included in the experimental group and 30 hypertensive patients in the control group.The average age of the populations were58±12 and 59±12 years and the ratios of male to female were 1.3.In the experimental group,BNP,CRP,NYHA classification,ventricular septal thickness,left atrial diameter,and the incidence of mitral leaflet systolic forward motion were all higher than those in the control group,and the difference was statistically significant.A total of 626 positive ion model metabolites and 393 negative ion model metabolites were identified in 60 samples of the two groups.There were significant differences in 84 positive ion model metabolites which including 77 up-regulated metabolites and 7down-regulated metabolites,while 48 negative ion model metabolites were significantly different,including 44 up-regulated metabolites and 4 down-regulated metabolites.There were significant differences in metabolites such as Ethyl caffeate,Pentadecanoic Acid,N-lactoyl-phenylalanine,Taurocholicacid(TC)and Glycocholicacid(GCA).Primary bile acid biosynthesis and Cholesterol metabolism are significant enrichment pathways of differential metabolites.TC and GCA are repeatedly enriched in the above metabolic pathways.According to the 17-segment division of the American Heart Association,the hearts of the two groups were divided into 480 segments,137 segments(28.84%)of hypertrophic myocardium and 343 segments(71.16%)of non-hypertrophic segments in the experimental group.103 segments(75.2%)were the most common.The Native T1 and ECV of the whole myocardium in the experimental group were higher than those in the control group(Native T1 t = 10.93,P < 0.001,ECV t = 9.564,P <0.001).In the experimental group,the Native T1 and ECV in the hypertrophic segment were higher than those in the non-hypertrophic segment(t = 11.538 P <0.001;t= 12.408 P < 0.001).According to whether the left ventricular outflow tract was obstructed or the anterior mitral valve moved forward(SAM),the experimental group was divided into obstructive type in 13 cases(43.3%)and non-obstructive type in 17 cases(56.7%).The Native T1 and ECV of obstructive and non-obstructive myocardium were higher than those of the control group(Native T1 t = 11.541,P < 0.001,ECV t = 6.564,P <0.001).The Native T1,Post T1 and ECV of the hypertrophic and non-hypertrophic segments of the obstructive patients were higher than those of the non-obstructive patients(hypertrophic segments Native T1 t=2.515,P=0.013;Post T1 t=4.958,P<0.001;ECV t=2.649,P=0.009;non-hypertrophic segments Native T1 t=3.469,P=0.001;Post T1 t=4.625,P<0.001;ECV t=2.735,P<0.001).In the obstruction group,the Native T1 and ECV of the hypertrophic segment were higher than those of the non-hypertrophic segment(Native T1 t=7.433,P<0.001,ECV t=7.158,P=0.012),the Native T1,Post T1 and ECV of the hypertrophic segment were higher than those of the non-hypertrophic segment in the non-obstruction group(Native T1 t=0.132 P <0.001,Post T1 t=2.184,P=0.030,ECV t=13.518,P<0.001).According to the existence of LGE,the experimental group was divided into 25 cases of LGE positive type(83.3%)and 5 cases of LGE negative type(16.7%).The Native T1 and ECV value of LGE positive and LGE negative myocardium were higher than those of the control group(Native T1 t = 6.759,P < 0.001,ECV t =9.374,P<0.001).The Native T1 and ECV of hypertrophic segments and non-hypertrophic segments in LGE positive group were higher than those in negative group(hypertrophic segments Native T1 t=7.906,P<0.001,ECV t=2.537,P=0.012;non-hypertrophic segments Native T1 t=2.945,P=0.003,ECV t=12.373,P<0.001).In the LGE positive group,the Native T1 and ECV in the hypertrophic segments were higher than those in the non-hypertrophic segments(Native T1 t=7.906,P<0.001;ECV t=2.537,P=0.012),and the ECV in the hypertrophic segments was higher than that in the non-hypertrophic segments in the LGE negative group(t=2.347,P=0.020).BNP,LVEF and Left Ventricular Mass Index(LVMI)were independently predictive of primary and secondary endpoint events in HCM patients(P<0.05),CRP,diuretic using,LVESD were independently predictive of primary endpoint events(P<0.05),and LAD was independently predictive of secondary endpoint events(P<0.05).In Kaplan-Meier survival analysis,the incidence of primary endpoint events was significantly increased with increases in BNP,CRP,LVESD,myocardial mass index,and ECV(P < 0.05).With the decrease of LVEF,the incidence of primary endpoint events was significantly increased(P<0.05).Conclusion(s): Ethyl caffeate,Pentadecanoic Acid、N-lactoyl-phenylalanine、TC and GCA can be used as new biomarkers in patients with HCM for further study.TC and GCA are repeatedly enriched in the primary bile acid synthesis pathway and cholesterol metabolism pathway,which may become new targets for regulating the progression of hypertrophic cardiomyopathy.CMR T1 mapping and ECV can be used to quantitatively evaluate myocardial fibrosis in patients with HCM,and ECV is more effective in the early diagnosis of myocardial fibrosis.LVEF and LVESD can be used as risk factors to evaluate the end point events of patients with HCM and affect the prognosis of the disease. |
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