Advertisement

Metabolic signatures in pericardial fluid and serum are associated with new-onset atrial fibrillation after isolated coronary artery bypass grafting

  • Author Footnotes
    1 Yunxiao Yang and Zhiyong Du contributed equally to this work.
    Yunxiao Yang
    Footnotes
    1 Yunxiao Yang and Zhiyong Du contributed equally to this work.
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Author Footnotes
    1 Yunxiao Yang and Zhiyong Du contributed equally to this work.
    Zhiyong Du
    Footnotes
    1 Yunxiao Yang and Zhiyong Du contributed equally to this work.
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Meng Fang
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
    Search for articles by this author
  • Ying Ma
    Affiliations
    National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, State Key Laboratory of Dao-di Herbs, Beijing, China
    Search for articles by this author
  • Yuhua Liu
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Tianguang Wang
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Zhongyi Han
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Zhan Peng
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Yilin Pan
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Haokai Qin
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Yanwen Qin
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Yong Jiang
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
    Search for articles by this author
  • Pengfei Tu
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
    Search for articles by this author
  • Xiaoyu Guo
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
    Search for articles by this author
  • Yingyuan Lu
    Correspondence
    Reprint requests: YINGYUAN Lu, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
    Search for articles by this author
  • Xiubin Yang
    Correspondence
    Reprint requests: XIUBIN Yang and KUN Hua, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Kun Hua
    Correspondence
    Reprint requests: XIUBIN Yang and KUN Hua, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
    Affiliations
    Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
    Search for articles by this author
  • Author Footnotes
    1 Yunxiao Yang and Zhiyong Du contributed equally to this work.
Published:January 10, 2023DOI:https://doi.org/10.1016/j.trsl.2023.01.001

      ABSTRACT

      Postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass grafting (CABG) procedures. However, the molecular mechanism of POAF remains poorly understood, hence the absence of effective prevention strategies. Here we used targeted metabolomics on pericardial fluid and serum samples from CABG patients to investigate POAF-associated metabolic alterations and related risk prediction of new-onset AF. Nine differential metabolites in various metabolic pathways were found in both pericardial fluid and serum samples from patients with POAF and without POAF. By using machine learning algorithms and regression models, a 4-metabolite (aceglutamide, ornithine, methionine, and arginine) risk prediction model was constructed and showed accurate performance in predicting POAF in both discovery and validation sets. This work extends the metabolic insights of the cardiac microenvironment and blood in patients with POAF and paves the way for the use of targeted metabolomics for predicting POAF in patients with CABG surgery.

      Abbreviations:

      AF (atrial fibrillation), AUC (area under curve), BMI (body mass index), CABG (coronary artery bypass grafting), DMs (differential metabolites), FDR (false discovery rate), fT3 (free triiodothyronine), fT4 (free thyroxine), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), LP(a) (lipoprotein-a), LVEF (left ventricular ejection fraction), PF (pericardial fluid), PCA (principal component analysis), PLS-DA (partial least squares discriminate analysis), POAF (postoperative atrial fibrillation), ROC (receiver operating curve), sdLDL-C (small dense low-density lipoprotein cholesterol), TC (total cholesterol), TG (triglyceride), TSH (thyroid stimulating hormone)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      REFERENCES

        • Dobrev D
        • Aguilar M
        • Heijman J
        • Guichard JB
        • Nattel S.
        Postoperative atrial fibrillation: mechanisms, manifestations and management.
        Nat Rev Cardiol. 2019; 16: 417-436
        • Eikelboom R
        • Sanjanwala R
        • Le ML
        • Yamashita MH
        • Arora RC.
        Postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis.
        Ann Thorac Surg. 2021; 111: 544-554
        • LaPar DJ
        • Speir AM
        • Crosby IK
        • et al.
        Postoperative atrial fibrillation significantly increases mortality, hospital readmission, and hospital costs.
        Ann Thorac Surg. 2014; 98: 527-533
        • Turan A
        • Duncan A
        • Leung S
        • et al.
        Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial.
        Lancet. 2020; 396: 177-185
        • Burrage PS
        • Low YH
        • Campbell NG
        • O'Brien B.
        New-onset atrial fibrillation in adult patients after cardiac surgery.
        Curr Anesthesiol Rep. 2019; 9: 174-193
        • King M
        • Stambulic T
        • Kirupaharan S
        • et al.
        Galectin-3 as a predictor of post cardiac surgery atrial fibrillation: a scoping review.
        Curr Probl Cardiol. 2022; 47101314
        • Khan MS
        • Yamashita K
        • Sharma V
        • et al.
        Perioperative biomarkers predicting postoperative atrial fibrillation risk after coronary artery bypass grafting: a narrative review.
        J Cardiothorac Vasc Anesth. 2020; 34: 1933-1941
        • Qureshi M
        • Ahmed A
        • Massie V
        • Marshall E
        • Harky A
        Determinants of atrial fibrillation after cardiac surgery.
        Rev Cardiovasc Med. 2021; 22: 329-341
        • DeBerardinis RJ
        • Keshari KR.
        Metabolic analysis as a driver for discovery, diagnosis, and therapy.
        Cell. 2022; 185: 2678-2689
        • Würtz P
        • Havulinna AS
        • Soininen P
        • et al.
        Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.
        Circulation. 2015; 131: 774-785
        • Floegel A
        • Kühn T
        • Sookthai D
        • et al.
        Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts.
        Eur J Epidemiol. 2018; 33: 55-66
        • Razquin C
        • Ruiz-Canela M
        • Toledo E
        • et al.
        Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet.
        Am J Clin Nutr. 2021; 114: 1646-1654
        • Suffee N
        • Baptista E
        • Piquereau J
        • et al.
        Impacts of a high fat diet on the metabolic profile and the phenotype of atrial myocardium in mice.
        Cardiovasc Res. 2022; 118 (9): 3126-3139
        • Zuo K
        • Fang C
        • Liu Z
        • et al.
        Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling.
        Int J Biol Sci. 2022; 18: 4219-4232
        • Li XY
        • Hou HT
        • Chen HX
        • et al.
        Preoperative plasma biomarkers associated with atrial fibrillation after coronary artery bypass surgery.
        J Thorac Cardiovasc Surg. 2021; 162: 851-863
        • Trindade F
        • Vitorino R
        • Leite-Moreira A
        • Falcão-Pires I.
        Pericardial fluid: an underrated molecular library of heart conditions and a potential vehicle for cardiac therapy.
        Basic Res Cardiol. 2019; 114: 10
        • Buoro S
        • Tombetti E
        • Ceriotti F
        • et al.
        What is the normal composition of pericardial fluid?.
        Heart. 2021; 107: 1584-1590
        • Imazio M
        • Biondo A
        • Ricci D
        • et al.
        Contemporary biochemical analysis of normal pericardial fluid.
        Heart. 2020; 106: 541-544
        • Butts B
        • Goeddel LA
        • George DJ
        • et al.
        Increased inflammation in pericardial fluid persists 48 hours after cardiac surgery.
        Circulation. 2017; 136: 2284-2286
        • Nakamura T
        • Azuma A
        • Sawada T
        • et al.
        Brain natriuretic peptide concentration in pericardial fluid is independently associated with atrial fibrillation after off-pump coronary artery bypass surgery.
        Coron Artery Dis. 2007; 18: 253-258
        • Manghelli JL
        • Kelly MO
        • Carter DI
        • et al.
        Pericardial mitochondrial DNA levels are associated with atrial fibrillation after cardiac surgery.
        Ann Thorac Surg. 2021; 111: 1593-1600
        • Lang RM
        • Badano LP
        • Mor-Avi V
        • et al.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        J Am Soc Echocardiogr. 2015; 28: 1-39
        • Al-Khatib SM
        • Hellkamp AS
        • Fonarow GC
        • et al.
        Association between prophylactic implantable cardioverter-defibrillators and survival in patients with left ventricular ejection fraction between 30% and 35%.
        Jama. 2014; 311: 2209-2215
        • Fatehi Hassanabad A
        • Zarzycki A
        • Deniset JF
        • Fedak PW
        An overview of human pericardial space and pericardial fluid.
        Cardiovasc Pathol. 2021; 53107346
        • Anderson EJ
        • Efird JT
        • Davies SW
        • et al.
        Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.
        J Am Heart Assoc. 2014; 3e000713
        • Antoniades C
        • Demosthenous M
        • Reilly S
        • et al.
        Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment.
        J Am Coll Cardiol. 2012; 59: 60-70
        • Kourliouros A
        • Yin X
        • Didangelos A
        • et al.
        Substrate modifications precede the development of atrial fibrillation after cardiac surgery: a proteomic study.
        Ann Thorac Surg. 2011; 92: 104-110
        • Jayaram R
        • Goodfellow N
        • Zhang MH
        • et al.
        Molecular mechanisms of myocardial nitroso-redox imbalance during on-pump cardiac surgery.
        Lancet. 2015; 385: S49
        • Lee MY
        • Lin YR
        • Tu YS
        • et al.
        Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials.
        J Biomed Sci. 2017; 24: 18
        • Bai K
        • Jiang L
        • Zhu S
        • et al.
        Dimethylglycine sodium salt protects against oxidative damage and mitochondrial dysfunction in the small intestines of mice.
        Int J Mol Med. 2019; 43: 2199-2211
        • Martínez Y
        • Li X
        • Liu G
        • et al.
        The role of methionine on metabolism, oxidative stress, and diseases.
        Amino Acids. 2017; 49: 2091-2098
        • Zhong H
        • Yuan P
        • Li Y
        • et al.
        Methionine protects mammary cells against oxidative stress through producing s-adenosylmethionine to maintain mTORC1 signaling activity.
        Oxid Med Cell Longev. 2021; 20215550196
        • Goni L
        • Razquin C
        • Toledo E
        • et al.
        Arginine catabolism metabolites and atrial fibrillation or heart failure risk: two case-control studies within the PREDIMED trial.
        Am J Clin Nutr. 2022; 116: 653-663
        • Liang M
        • Wang Z
        • Li H
        • et al.
        l-Arginine induces antioxidant response to prevent oxidative stress via stimulation of glutathione synthesis and activation of Nrf2 pathway.
        Food Chem Toxicol. 2018; 115: 315-328
        • Morris CR
        • Brown LAS
        • Reynolds M
        • et al.
        Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain.
        Blood. 2020; 136: 1402-1406
        • Shin S
        • Gombedza FC
        • Bandyopadhyay BC.
        l-ornithine activates Ca(2+) signaling to exert its protective function on human proximal tubular cells.
        Cell Signal. 2020; 67109484
        • Manfrini O
        • Cenko E
        • Ricci B
        • Bugiardini R.
        Post cardiovascular surgery atrial fibrillation. Biomarkers determining prognosis.
        Curr Med Chem. 2019; 26: 916-924
        • Alexandre J
        • Saloux E
        • Chequel M
        • et al.
        Preoperative plasma aldosterone and the risk of atrial fibrillation after coronary artery bypass surgery: a prospective cohort study.
        J Hypertens. 2016; 34: 2449-2457
        • Thorén E
        • Hellgren L
        • Jidéus L
        • Ståhle E.
        Prediction of postoperative atrial fibrillation in a large coronary artery bypass grafting cohort.
        Interact Cardiovasc Thorac Surg. 2012; 14: 588-593
        • Verdejo H
        • Roldan J
        • Garcia L
        • et al.
        Systemic vascular cell adhesion molecule-1 predicts the occurrence of post-operative atrial fibrillation.
        Int J Cardiol. 2011; 150: 270-276