Plasma Metabolomics And Novel Biomarkers Of Cardiac Specificity In Patients With Heart Failure

Background:Dilated cardiomyopathy(DCM)and ischemic cardiomyopathy(ICM)are common causes of heart failure(HF).Though they share similar clinical characteristics,their differential effects on cardiovascular metabolomics have yet to be elucidated.Methods:In this study,we applied a comprehensive metabolomics platform to plasma samples of HF patients with different etiology(38 patients with DCM and 18 patients with ICM)and 20 healthy controls.Results:Significant differences in metabolomics profiling were shown among two cardiomyopathy groups and healthy controls.233 dysregulated metabolites were identified between DCM versus healthy controls,and 204 dysregulated metabolites between ICM patients and healthy controls.They have 140 metabolites in common,with fold-changes in the same direction in both groups.Pathway analysis found the commonalities of HF pathways as well as disease-specific metabolic signatures.In addition,we found that a combination panel of 6 metabolites including 1-pyrroline-2-carboxylate,norvaline,lysophosphatidylinositol(16:0/0:0),phosphatidylglycerol(6:0/8:0),fatty acid esters of hydroxy fatty acid(24:1)and phosphatidylcholine(18:0/18:3)may have the potential to differentiate patients with DCM and ICM.Conclusion:This study revealed significant different plasma metabolomics signatures with different cardiomyopathy.And we developed a plasma metabolites panel that may have the potential to differentiate patients with DCM and ICM.The commonalities as well as disease-specific metabolic signatures in DCM and ICM could provide more insights into disease underlying mechanisms as well as personalized therapy strategy.Introduction:Current strategy for implantable cardioverter-defibrillator implantation had brought significant clinical benefits,but are not perfect.A better risk stratification to identify appropriate patients who can truly benefit from implantable cardioverter-defibrillator(ICD)implantation is urgently needed.Metabolomics provide a promising tool to comprehensively screen and identify novel biomarkers.This study aimed to assess whether dysregulated metabolites were associated with the occurrence life-threatening ventricular arrhythmia(LTVA)and to discover novel metabolites that could serve as biomarkers for early prediction.Methods:In this study,we prospectively recruited 72 patients who scheduled for ICD implantation and collected their plasma samples before the surgery.And we assessed the plasma samples using a non-targeted metabolomics platform.Results:We found 23 metabolites were significantly associated with occurrence of LTVA independent of age,smoker,second prevention and CK-MB.Pathway analysis revealed perturbations in glycine,serine,and threonine metabolism and branched chain amino acid metabolism were associated with LTVA.We also showed that a panel of six selected metabolites potentially predict occurrence of LTVA with an area under the receiver operating characteristic curve of 0.82,0.80,0.78 and 0.86 at six months,1 year,2years and 3years after the ICD implantation.Conclusion:Our study demonstrated a panel of six-metabolite could predict the occurrence of LTVA in patients with ICD implantation.More studies are needed to shed light on the potential clinical use and underlying biological mechanisms.Introduction:Heart failure(HF)is a complicated syndrome with an estimation of more than 37.7 million affected individuals globally.Biomarkers plays a vital role in HF management.However,previous research indicated that some novel biomarkers may not cardiac-specific and thus hinder its clinical use.The origin of these novel biomarkers was largely unknown.Methods:In this study,we selected classical biomarker B-type natriuretic peptide(BNP)and 5 novel biomarkers including galectin-3,soluble suppression of tumorigenicity 2(sST2),tissue inhibitor of metalloproteinase 1(TIMP-1),growth differentiation factor 15(GDF-15)and myeloperoxidase(MPO).We simultaneously collected blood from artery and coronary sinus in 30 HF patients who receive cardiac resynchronization therapy(CRT)device implantation and 10 non-HF controls.And we calculated the trans-coronary changes of these biomarkers.In addition,in order to investigate their origin,we conducted a pacing-induced HF canine model and assessed their production in different parts of heart as well as in other organs.Results:We found BNP,Gal-3 and TIMP-1 were elevated across heart in patients with HF rather than non-HF controls.While,the level of sST2,GDF-15 and MPO did not changed significantly across heart.The tans-coronary changes were correlated with cardiac function parameters such as left ventricular end-diastolic dimension(LVEDD)and left ventricular ejection fraction(LVEF).These findings were then verified in heart tissues from HF canine models,which showed elevated production of BNP,Gal-3 and TIMP-1.Conclusion:In this study,we provided direct evidence of the trans-coronary changes of 6 biomarkers in patients with HF.And we also investigated its intracardiac productions.This study may provide us with a better understanding of the biology of these biomarkers and shed light on the its application in clinical practice.