{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:59:13Z","timestamp":1789070353441,"version":"build-2803163510"},"reference-count":145,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Heart failure (HF) is a clinical condition defined by structural and functional abnormalities in the heart that gradually result in reduced cardiac output (HFrEF) and\/or increased cardiac pressures at rest and under stress (HFpEF). The presence of asymptomatic individuals hampers HF identification, resulting in delays in recognizing patients until heart dysfunction is manifested, thus increasing the chance of poor prognosis. Given the recent advances in metabolomics, in this review we dissect the main alterations occurring in the metabolic pathways behind the decrease in cardiac function caused by HF. Indeed, relevant preclinical and clinical research has been conducted on the metabolite connections and differences between HFpEF and HFrEF. Despite these promising results, it is crucial to note that, in addition to identifying single markers and reliable threshold levels within the healthy population, the introduction of composite panels would strongly help in the identification of those individuals with an increased HF risk. That said, additional research in the field is required to overcome the current drawbacks and shed light on the pathophysiological changes that lead to HF. Finally, greater collaborative data sharing, as well as standardization of procedures and approaches, would enhance this research field to fulfil its potential.<\/jats:p>","DOI":"10.3390\/biom12070969","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T21:57:53Z","timestamp":1657576673000},"page":"969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Understanding How Heart Metabolic Derangement Shows Differential Stage Specificity for Heart Failure with Preserved and Reduced Ejection Fraction"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6023-8227","authenticated-orcid":false,"given":"Federico","family":"Ferro","sequence":"first","affiliation":[{"name":"Department of Medical, Surgery and Health Sciences, University of Trieste, 34125 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renza","family":"Spelat","sequence":"additional","affiliation":[{"name":"Neurobiology Sector, International School for Advanced Studies (SISSA), 34136 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35122 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6990-9883","authenticated-orcid":false,"given":"Paolo","family":"Contessotto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35122 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/ejhf.1209","article-title":"Sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide levels in the general population","volume":"20","author":"Suthahar","year":"2018","journal-title":"Eur. J. Heart Fail"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1002\/ejhf.1944","article-title":"Risk of bias in studies investigating novel diagnostic biomarkers for heart failure with preserved ejection fraction. A systematic review","volume":"22","author":"Henkens","year":"2020","journal-title":"Eur. J. Heart Fail"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s12265-013-9472-1","article-title":"Biomarkers of diastolic dysfunction and myocardial fibrosis: Application to heart failure with a preserved ejection fraction","volume":"6","author":"Zile","year":"2013","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.pharmthera.2017.08.001","article-title":"Cardiac metabolism-A promising therapeutic target for heart failure","volume":"182","author":"Noordali","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.cmet.2018.04.015","article-title":"The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase","volume":"27","author":"White","year":"2018","journal-title":"Cell Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0003-9861(92)90243-P","article-title":"Ethanol and oleate inhibition of \u03b1-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes","volume":"299","author":"Hu","year":"1992","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jacc.2013.02.092","article-title":"A novel paradigm for heart failure with preserved ejection fraction: Comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation","volume":"62","author":"Paulus","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3390\/cells9010242","article-title":"Cellular and molecular differences between HFpEF and HFrEF: A step ahead in an improved pathological understanding","volume":"9","author":"Simmonds","year":"2020","journal-title":"Cells"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eaaz5380","DOI":"10.1126\/scitranslmed.aaz5380","article-title":"Elastin-like recombinamers-based hydrogel modulates post-ischemic remodeling in a non-transmural myocardial infarction in sheep","volume":"13","author":"Contessotto","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"120906","DOI":"10.1016\/j.biomaterials.2021.120906","article-title":"Therapies to prevent post-infarction remodelling: From repair to regeneration","volume":"275","author":"Contessotto","year":"2021","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"879214","DOI":"10.3389\/fphys.2022.879214","article-title":"Mimicking metabolic disturbance in establishing animal models of heart failure with preserved ejection fraction","volume":"13","author":"Li","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0323-2","article-title":"Heart failure with preserved ejection fraction: Present status and future directions","volume":"51","author":"Yoon","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1093\/cvr\/cvz161","article-title":"Small animal models of heart failure","volume":"115","author":"Riehle","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12471-016-0815-9","article-title":"Animal models of heart failure with preserved ejection fraction","volume":"24","author":"Heinonen","year":"2016","journal-title":"Neth. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00395-005-0549-0","article-title":"Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart","volume":"101","author":"Degens","year":"2006","journal-title":"Basic Res. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10020-018-0005-x","article-title":"Uncoupling of glycolysis from glucose oxidation accompanies the development of heart failure with preserved ejection fraction","volume":"24","author":"Fillmore","year":"2018","journal-title":"Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCHEARTFAILURE.111.966127","article-title":"Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension","volume":"6","author":"Mizuno","year":"2013","journal-title":"Circ. Heart Fail"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1161\/CIRCHEARTFAILURE.114.001469","article-title":"Energy metabolic reprogramming in the hypertrophied and early stage failing heart: A multisystems approach","volume":"7","author":"Lai","year":"2014","journal-title":"Circ. Heart Fail"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"H1103","DOI":"10.1152\/ajpheart.00636.2012","article-title":"ANG II causes insulin resistance and induces cardiac metabolic switch and inefficiency: A critical role of PDK4","volume":"304","author":"Mori","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1161\/CIRCHEARTFAILURE.112.966705","article-title":"Agonist-induced hypertrophy and diastolic dysfunction are associated with selective reduction in glucose oxidation: A metabolic contribution to heart failure with normal ejection fraction","volume":"5","author":"Mori","year":"2012","journal-title":"Circ. Heart Fail"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.yjmcc.2013.07.010","article-title":"Impact of the renin-angiotensin system on cardiac energy metabolism in heart failure","volume":"63","author":"Mori","year":"2013","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.yjmcc.2006.06.004","article-title":"Overexpression of angiotensinogen in the myocardium induces downregulation of the fatty acid oxidation pathway","volume":"41","author":"Pellieux","year":"2006","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1161\/01.CIR.94.11.2837","article-title":"Fatty acid oxidation enzyme gene expression is downregulated in the failing heart","volume":"94","author":"Sack","year":"1996","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12035","DOI":"10.1038\/s41598-018-30616-1","article-title":"Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure","volume":"8","author":"Umbarawan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1093\/cvr\/cvy063","article-title":"Glucose is preferentially utilized for biomass synthesis in pressure-overloaded hearts: Evidence from fatty acid-binding protein-4 and -5 knockout mice","volume":"114","author":"Umbarawan","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1126\/science.abc8861","article-title":"Comprehensive quantification of fuel use by the failing and nonfailing human heart","volume":"370","author":"Murashige","year":"2020","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e003190","DOI":"10.1161\/JAHA.115.003190","article-title":"Metabolomic profiling identifies novel circulating biomarkers of mitochondrial dysfunction differentially elevated in heart failure with preserved versus reduced ejection fraction: Evidence for shared metabolic impairments in clinical heart failure","volume":"5","author":"Hunter","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.cjca.2020.03.024","article-title":"Quantitative metabolomics reveals heart failure with midrange ejection fraction as a distinct phenotype of heart failure","volume":"37","author":"Zhao","year":"2021","journal-title":"Can. J. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.jacc.2015.02.018","article-title":"Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: Diagnostic and prognostic value of metabolomics","volume":"65","author":"Cheng","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1536\/ihj.20-053","article-title":"Decreases in circulating concentrations of short-chain acylcarnitines are associated with systolic function improvement after decompensated heart failure","volume":"61","author":"Chen","year":"2020","journal-title":"Int. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.cardfail.2020.07.010","article-title":"Metabolomic profile in HFpEF vs HFrEF patients","volume":"26","author":"Hage","year":"2020","journal-title":"J. Card. Fail"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zordoky, B.N., Sung, M.M., Ezekowitz, J., Mandal, R., Han, B., Bjorndahl, T.C., Bouatra, S., Anderson, T., Oudit, G.Y., and Wishart, D.S. (2015). Metabolomic fingerprint of heart failure with preserved ejection fraction. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124844"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1001\/jamacardio.2017.1239","article-title":"Sildenafil treatment in heart failure with preserved ejection fraction: Targeted metabolomic profiling in the relax trial","volume":"2","author":"Wang","year":"2017","journal-title":"JAMA Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10560","DOI":"10.1096\/fj.202000495RR","article-title":"Deficit of resolution receptor magnifies inflammatory leukocyte directed cardiorenal and endothelial dysfunction with signs of cardiomyopathy of obesity","volume":"34","author":"Tourki","year":"2020","journal-title":"FASEB J."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ferro, F., Ouill\u00e9, A., Tran, T.A., Fontanaud, P., Bois, P., Babuty, D., Labarthe, F., and Le Guennec, J.Y. (2012). Long-chain acylcarnitines regulate the hERG channel. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041686"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1096\/fj.14-255901","article-title":"Acylcarnitines: Potential implications for skeletal muscle insulin resistance","volume":"29","author":"Aguer","year":"2015","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jacc.2015.10.079","article-title":"Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support","volume":"67","author":"Ahmad","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"H768","DOI":"10.1152\/ajpheart.00820.2016","article-title":"Circulating acylcarnitine profile in human heart failure: A surrogate of fatty acid metabolic dysregulation in mitochondria and beyond","volume":"313","author":"Ruiz","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"577856","DOI":"10.3389\/fphys.2020.577856","article-title":"Long-chain acylcarnitines and cardiac excitation-contraction coupling: Links to arrhythmias","volume":"11","author":"Krause","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.hfc.2017.08.011","article-title":"Metabolic biomarkers in heart failure","volume":"14","author":"Albert","year":"2018","journal-title":"Heart Fail Clin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/eurjhf\/hfs172","article-title":"Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction","volume":"15","author":"Stride","year":"2013","journal-title":"Eur. J. Heart Fail"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1042\/CS20200128","article-title":"Short-chain fatty acid, acylation and cardiovascular diseases","volume":"134","author":"Chen","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1161\/CIRCULATIONAHA.120.052671","article-title":"Short-chain fatty acids outpace ketone oxidation in the failing heart","volume":"143","author":"Carley","year":"2021","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1161\/CIRCULATIONAHA.115.017355","article-title":"The failing heart relies on ketone bodies as a fuel","volume":"133","author":"Aubert","year":"2016","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e124079","DOI":"10.1172\/jci.insight.124079","article-title":"The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense","volume":"4","author":"Horton","year":"2019","journal-title":"JCI Insight"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12933-019-0806-4","article-title":"Targeting the glucagon receptor improves cardiac function and enhances insulin sensitivity following a myocardial infarction","volume":"18","author":"Karwi","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1161\/CIRCRESAHA.121.318241","article-title":"Cardiac energy metabolism in heart failure","volume":"128","author":"Lopaschuk","year":"2021","journal-title":"Circ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.molmet.2014.07.010","article-title":"Cardiomyocyte-specific deficiency of ketone body metabolism promotes accelerated pathological remodeling","volume":"3","author":"Schugar","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1126\/science.1227166","article-title":"Suppression of oxidative stress by \u03b2-hydroxybutyrate, an endogenous histone deacetylase inhibitor","volume":"339","author":"Shimazu","year":"2013","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm.3804","article-title":"The ketone metabolite \u03b2-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease","volume":"21","author":"Youm","year":"2015","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.cjca.2017.03.009","article-title":"Complex energy metabolic changes in heart failure with preserved ejection fraction and heart failure with reduced ejection fraction","volume":"33","author":"Lopaschuk","year":"2017","journal-title":"Can. J. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1161\/CIRCRESAHA.120.317933","article-title":"Targeting mitochondria-inflammation circuit by \u03b2-hydroxybutyrate mitigates HFpEF","volume":"128","author":"Deng","year":"2021","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1161\/CIRCULATIONAHA.115.017545","article-title":"Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure","volume":"133","author":"Bedi","year":"2016","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Du, Z., Shen, A., Huang, Y., Su, L., Lai, W., Wang, P., Xie, Z., Xie, Z., Zeng, Q., and Ren, H. (2014). 1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088102"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e13468","DOI":"10.1111\/eci.13468","article-title":"Association of beta-hydroxybutyrate with development of heart failure: Sex differences in a Dutch population cohort","volume":"51","author":"Westenbrink","year":"2021","journal-title":"Eur J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/0735-1097(96)00214-8","article-title":"Blood ketone bodies in congestive heart failure","volume":"28","author":"Lommi","year":"1996","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e004953","DOI":"10.1161\/CIRCHEARTFAILURE.118.004953","article-title":"Increased cardiac uptake of ketone bodies and free fatty acids in human heart failure and hypertrophic left ventricular remodeling","volume":"11","author":"Voros","year":"2018","journal-title":"Circ. Heart Fail"},{"key":"ref_58","first-page":"100432","article-title":"Circulating acetoacetate is associated with poor prognosis in heart failure patients","volume":"25","author":"Yokokawa","year":"2019","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3707","DOI":"10.1002\/ehf2.12923","article-title":"Metabolomic signatures of cardiac remodelling and heart failure risk in the community","volume":"7","author":"Andersson","year":"2020","journal-title":"ESC Heart Fail"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1046\/j.1365-2796.1997.00187.x","article-title":"Heart failure ketosis","volume":"242","author":"Lommi","year":"1997","journal-title":"J. Intern. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.cmet.2016.12.022","article-title":"Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics","volume":"25","author":"Puchalska","year":"2017","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature13909","article-title":"Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS","volume":"515","author":"Chouchani","year":"2014","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6743","DOI":"10.1038\/s41598-019-42937-w","article-title":"Serum concentrations of citrate, tyrosine, 2- and 3- hydroxybutyrate are associated with increased 3-month mortality in acute heart failure patients","volume":"9","author":"Stryeck","year":"2019","journal-title":"Sci Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"E1046","DOI":"10.1152\/ajpendo.00097.2018","article-title":"Cardiac branched-chain amino acid oxidation is reduced during insulin resistance in the heart","volume":"315","author":"Fillmore","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1021\/acs.jproteome.9b00002","article-title":"Time series characteristics of serum branched-chain amino acids for early diagnosis of chronic heart failure","volume":"18","author":"Li","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1161\/CIRCHEARTFAILURE.114.001151","article-title":"Metabolomic analysis of pressure-overloaded and infarcted mouse hearts","volume":"7","author":"Sansbury","year":"2014","journal-title":"Circ. Heart Fail"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/CIRCULATIONAHA.115.020226","article-title":"Catabolic defect of branched-chain amino acids promotes heart failure","volume":"133","author":"Sun","year":"2016","journal-title":"Circulation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.chroma.2014.08.028","article-title":"Metabonomic study of chronic heart failure and effects of chinese herbal decoction in rats","volume":"1362","author":"Guo","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nm.4057","article-title":"A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance","volume":"22","author":"Jang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.metabol.2015.05.014","article-title":"Octanoic acid promotes branched-chain amino acid catabolisms via the inhibition of hepatic branched-chain alpha-keto acid dehydrogenase kinase in rats","volume":"64","author":"Kadota","year":"2015","journal-title":"Metabolism"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e5012","DOI":"10.1002\/bmc.5012","article-title":"Plasma amino acid metabolomic pattern in heart failure patients with either preserved or reduced ejection fraction: The relation to established risk variables and prognosis","volume":"35","author":"Saleem","year":"2020","journal-title":"Biomed. Chromatogr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3784589","DOI":"10.1155\/2018\/3784589","article-title":"Amino acid-based metabolic panel provides robust prognostic value additive to b-natriuretic peptide and traditional risk factors in heart failure","volume":"2018","author":"Wang","year":"2018","journal-title":"Dis. Markers"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12967-017-1215-7","article-title":"Blood metabolomic fingerprint is distinct in healthy coronary and in stenosing or microvascular ischemic heart disease","volume":"15","author":"Deidda","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"H1538","DOI":"10.1152\/ajpheart.00281.2004","article-title":"Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation","volume":"287","author":"Chandler","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.yjmcc.2019.07.007","article-title":"Remodeling of substrate consumption in the murine sTAC model of heart failure","volume":"134","author":"Turer","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/FJC.0000000000000719","article-title":"Sirtuin 3, endothelial metabolic reprogramming, and heart failure with preserved ejection fraction","volume":"74","author":"Zeng","year":"2019","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1161\/CIRCHEARTFAILURE.112.000228","article-title":"Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy","volume":"6","author":"Zhang","year":"2013","journal-title":"Circ. Heart Fail"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/s41418-020-00729-0","article-title":"Heart failure-emerging roles for the mitochondrial pyruvate carrier","volume":"28","author":"Eaton","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"E578","DOI":"10.1152\/ajpendo.00093.2009","article-title":"The Randle cycle revisited: A new head for an old hat","volume":"297","author":"Hue","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1006\/bbrc.1999.2068","article-title":"Role of troponin I isoform switching in determining the pH sensitivity of Ca2+ regulation in developing rabbit cardiac muscle","volume":"267","author":"Morimoto","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Contaifer, D., Buckley, L.F., Wohlford, G., Kumar, N.G., Morriss, J.M., Ranasinghe, A.D., Carbone, S., Canada, J.M., Trankle, C., and Abbate, A. (2019). Metabolic modulation predicts heart failure tests performance. PLoS ONE, 14.","DOI":"10.1101\/555417"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Desmoulin, F., Galinier, M., Trouillet, C., Berry, M., Delmas, C., Turkieh, A., Massabuau, P., Taegtmeyer, H., Smih, F., and Rouet, P. (2013). Metabonomics analysis of plasma reveals the lactate to cholesterol ratio as an independent prognostic factor of short-term mortality in acute heart failure. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060737"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ajem.2010.10.008","article-title":"Lactate in the acute phase of ST-elevation myocardial infarction treated with mechanical revascularization: A single-center experience","volume":"30","author":"Lazzeri","year":"2012","journal-title":"Am. J. Emerg. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Shibayama, J., Yuzyuk, T.N., Cox, J., Makaju, A., Miller, M., Lichter, J., Li, H., Leavy, J.D., Franklin, S., and Zaitsev, A.V. (2015). Metabolic remodeling in moderate synchronous versus dyssynchronous pacing-induced heart failure: Integrated metabolomics and proteomics study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118974"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2021.11866","article-title":"Metabolic remodeling in the right ventricle of rats with severe pulmonary arterial hypertension","volume":"23","author":"Sakao","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1139\/y87-067","article-title":"Competition between fatty acids and carbohydrate or ketone bodies as metabolic fuels for the isolated perfused heart","volume":"65","author":"Forsey","year":"1987","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"H1134","DOI":"10.1152\/ajpheart.00407.2014","article-title":"Propionate stimulates pyruvate oxidation in the presence of acetate","volume":"307","author":"Purmal","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1172\/JCI115008","article-title":"Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate","volume":"87","author":"Russell","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11897-016-0289-5","article-title":"Metabolic dysfunction in heart failure: Diagnostic, prognostic, and pathophysiologic insights from metabolomic profiling","volume":"13","author":"Hunter","year":"2016","journal-title":"Curr. Heart Fail Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1158\/2159-8290.CD-19-0959","article-title":"Selective alanine transporter utilization creates a targetable metabolic niche in pancreatic cancer","volume":"10","author":"Parker","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1007\/s11010-021-04159-5","article-title":"Comprehensive plasma metabolomic and lipidomic analyses reveal potential biomarkers for heart failure","volume":"476","author":"Zhou","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/clc.4960210904","article-title":"Potential cardiovascular applications of glutamate, aspartate, and other amino acids","volume":"21","author":"Arsenian","year":"1998","journal-title":"Clin. Cardiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e003755","DOI":"10.1161\/JAHA.116.003755","article-title":"Metabolites of glutamate metabolism are associated with incident cardiovascular events in the PREDIMED PREvenci\u00f3n con Dieta MEDiterr\u00e1nea (PREDIMED) trial","volume":"5","author":"Zheng","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s00380-020-01765-z","article-title":"Prognostic value of leucine\/phenylalanine ratio as an amino acid profile of heart failure","volume":"36","author":"Hiraiwa","year":"2021","journal-title":"Heart Vessel."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1007\/s00726-018-2649-9","article-title":"Simplified plasma essential amino acid-based profiling provides metabolic information and prognostic value additive to traditional risk factors in heart failure","volume":"50","author":"Wang","year":"2018","journal-title":"Amino Acids"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/2044-5040-1-13","article-title":"\u03b4-Sarcoglycan-deficient muscular dystrophy: From discovery to therapeutic approaches","volume":"1","author":"Blain","year":"2011","journal-title":"Skelet. Muscle"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/0022-2828(91)90165-I","article-title":"Decreased 1,2-diacylglycerol levels in myopathic hamster hearts during the development of heart failure","volume":"23","author":"Okumura","year":"1991","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.yjmcc.2012.09.002","article-title":"Mitochondria in cardiac hypertrophy and heart failure","volume":"55","author":"Rosca","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1111\/bph.12461","article-title":"First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics","volume":"171","author":"Szeto","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jacbts.2016.11.009","article-title":"Metabolic origins of heart failure","volume":"2","author":"Wende","year":"2017","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/1873-3468.12887","article-title":"The role of nonbilayer phospholipids in mitochondrial structure and function","volume":"592","author":"Neff","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.jacc.2017.11.067","article-title":"Activation of serine one-carbon metabolism by calcineurin A\u03b21 reduces myocardial hypertrophy and improves ventricular function","volume":"71","author":"Cogliati","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.bbadis.2017.11.009","article-title":"Serine prevented high-fat diet-induced oxidative stress by activating AMPK and epigenetically modulating the expression of glutathione synthesis-related genes","volume":"1864","author":"Zhou","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.jacc.2011.12.022","article-title":"Pulmonary hypertension associated with advanced systolic heart failure: Dysregulated arginine metabolism and importance of compensatory dimethylarginine dimethylaminohydrolase-1","volume":"59","author":"Shao","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1093\/eurheartj\/ehn360","article-title":"Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure","volume":"29","author":"Tang","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"H590","DOI":"10.1152\/ajpheart.00512.2019","article-title":"Gut microbiome of a porcine model of metabolic syndrome and HF-pEF","volume":"318","author":"Herisson","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Guo, F., Qiu, X., Tan, Z., Li, Z., and Ouyang, D. (2020). Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction. BMC Cardiovasc. Disord., 20.","DOI":"10.1186\/s12872-020-01669-w"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1016\/j.jacc.2017.10.064","article-title":"Trimethylamine-N-oxide and heart failure with reduced versus preserved ejection fraction","volume":"70","author":"Schuett","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41569-018-0108-7","article-title":"Dietary metabolism, the gut microbiome, and heart failure","volume":"16","author":"Tang","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.trsl.2020.08.007","article-title":"TMAO: How gut microbiota contributes to heart failure","volume":"228","author":"Zhang","year":"2021","journal-title":"Transl. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1017\/S0954422420000177","article-title":"Trimethylamine N-oxide: Heart of the microbiota-CVD nexus?","volume":"34","author":"Naghipour","year":"2021","journal-title":"Nutr. Res. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1017\/erm.2016.6","article-title":"The complex metabolism of trimethylamine in humans: Endogenous and exogenous sources","volume":"18","author":"Gaur","year":"2016","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"490","DOI":"10.3390\/toxins11090490","article-title":"TMA, A forgotten uremic toxin, but not TMAO, is involved in cardiovascular pathology","volume":"11","author":"Jaworska","year":"2019","journal-title":"Toxins Basel"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1161\/HYPERTENSIONAHA.115.05315","article-title":"Gut dysbiosis is linked to hypertension","volume":"65","author":"Yang","year":"2015","journal-title":"Hypertension"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"H475","DOI":"10.1152\/ajpheart.00573.2020","article-title":"The role of diet-derived short-chain fatty acids in regulating cardiac pressure overload","volume":"320","author":"Pakhomov","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e020654","DOI":"10.1161\/JAHA.120.020654","article-title":"The gut microbiome of heart failure with preserved ejection fraction","volume":"10","author":"Beale","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000064347","article-title":"Deoxycholic acid conjugates are muscarinic cholinergic receptor antagonists","volume":"65","author":"Raufman","year":"2002","journal-title":"Pharmacology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S1097-2765(00)80348-2","article-title":"Endogenous bile acids are ligands for the nuclear receptor FXR\/BAR","volume":"3","author":"Wang","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/sj.bjp.0703554","article-title":"On the in vitro vasoactivity of bile acids","volume":"131","author":"Ljubuncic","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.cardfail.2017.06.007","article-title":"Increased secondary\/primary bile acid ratio in chronic heart failure","volume":"23","author":"Mayerhofer","year":"2017","journal-title":"J. Card. Fail."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e12462","DOI":"10.1111\/1755-5922.12462","article-title":"TGR5 activation induces cytoprotective changes in the heart and improves myocardial adaptability to physiologic, inotropic, and pressure-induced stress in mice","volume":"36","author":"Eblimit","year":"2018","journal-title":"Cardiovasc. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.jacc.2011.10.880","article-title":"Ursodeoxycholic acid in patients with chronic heart failure: A double-blind, randomized, placebo-controlled, crossover trial","volume":"59","author":"Schefold","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"577526","DOI":"10.1016\/j.jneuroim.2021.577526","article-title":"Gut microbial metabolite TMAO portends prognosis in acute ischemic stroke","volume":"354","author":"Zhang","year":"2021","journal-title":"J. Neuroimmunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"H1060","DOI":"10.1152\/ajpheart.00646.2012","article-title":"Ketone body metabolism and cardiovascular disease","volume":"304","author":"Cotter","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_126","unstructured":"Berg, J.M., Tymoczko, J.L., and Stryer, L. (2007). Protein turnover and amino acid catabolism. Biochemistry, W H Freeman. [8th ed.]."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1038\/s41467-018-05362-7","article-title":"Glucose promotes cell growth by suppressing branched-chain amino acid degradation","volume":"9","author":"Shao","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1039\/c3mb70227h","article-title":"Metabolomic identification of diagnostic plasma biomarkers in humans with chronic heart failure","volume":"9","author":"Wang","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jjcc.2018.05.007","article-title":"Nutritional status of outpatients with chronic stable heart failure based on serum amino acid concentration","volume":"72","author":"Tsuji","year":"2018","journal-title":"J. Cardiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4948","DOI":"10.1111\/jcmm.13759","article-title":"Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation","volume":"22","author":"Zhenyukh","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1161\/CIRCRESAHA.111.246371","article-title":"Pyridine nucleotide regulation of cardiac intermediary metabolism","volume":"111","author":"Ussher","year":"2012","journal-title":"Circ. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA cycle metabolites control physiology and disease","volume":"11","author":"Chandel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"8632726","DOI":"10.1155\/2019\/8632726","article-title":"Amino acid-based metabolic profile provides functional assessment and prognostic value for heart failure outpatients","volume":"2019","author":"Wang","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1056\/NEJMra063052","article-title":"The failing heart-an engine out of fuel","volume":"356","author":"Neubauer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ijcard.2013.12.014","article-title":"The breathing heart-mitochondrial respiratory chain dysfunction in cardiac disease","volume":"171","author":"Schwarz","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrcardio.2016.203","article-title":"Expert consensus document: Mitochondrial function as a therapeutic target in heart failure","volume":"14","author":"Brown","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/ehf2.12453","article-title":"The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population","volume":"6","author":"Stenemo","year":"2019","journal-title":"ESC Heart Fail."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1161\/CIRCULATIONAHA.108.815944","article-title":"Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: Insights from the framingham heart study of the national heart, lung, and blood institute","volume":"119","author":"Lee","year":"2009","journal-title":"Circulation"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.jchf.2018.05.018","article-title":"The association of obesity and cardiometabolic traits with incident HFpEF and HFrEF","volume":"6","author":"Savji","year":"2018","journal-title":"JACC Heart Fail."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1161\/CIRCRESAHA.119.315889","article-title":"Targeting age-related pathways in heart failure","volume":"126","author":"Li","year":"2020","journal-title":"Circ. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2337\/dc17-0755","article-title":"The prognostic significance of diabetes and microvascular complications in patients with heart failure with preserved ejection fraction","volume":"41","author":"Sandesara","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1002\/ehf2.13124","article-title":"Heart failure in the last year: Progress and perspective","volume":"7","author":"Tomasoni","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.jacc.2019.12.049","article-title":"Menopause-related estrogen decrease and the pathogenesis of HFpEF: JACC review topic of the week","volume":"75","author":"Sabbatini","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1093\/eurheartj\/ehz835","article-title":"Sex differences in heart failure","volume":"40","author":"Lam","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000513545","article-title":"Metabolomics: The stethoscope for the twenty-first century","volume":"30","author":"Ashrafian","year":"2021","journal-title":"Med. Princ. Pract."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/7\/969\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:48:05Z","timestamp":1760140085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/7\/969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,11]]},"references-count":145,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["biom12070969"],"URL":"https:\/\/doi.org\/10.3390\/biom12070969","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,11]]}}}