{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:32:24Z","timestamp":1793367144452,"version":"4.5.0"},"reference-count":162,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","onlinejcf.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Cardiac Failure"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.cardfail.2026.09.029","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:50:23Z","timestamp":1791215423000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Comorbidity-Driven Interleukin-6-Mediated Systemic Inflammation Hypothesis of Heart Failure With Preserved Ejection Fraction: A Decade of Testing Ends in Disappointment"],"prefix":"10.1016","author":[{"given":"MILTON","family":"PACKER","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JAVED","family":"BUTLER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FAIEZ","family":"ZANNAD","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MUTHIAH","family":"VADUGANATHAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-0596","authenticated-orcid":false,"given":"BARRY A.","family":"BORLAUG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"22","key":"10.1016\/j.cardfail.2026.09.029_bib0001","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1056\/NEJM199111283252206","article-title":"Diastolic dysfunction in congestive heart failure","volume":"325","author":"Grossman","year":"1991","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0002","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1056\/NEJMoa032566","article-title":"Diastolic heart failure \u2013 abnormalities in active relaxation and passive stiffness of the left ventricle","volume":"350","author":"Zile","year":"2004","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0003","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1056\/NEJM198501313120504","article-title":"Hypertensive hypertrophic cardiomyopathy of the elderly","volume":"312","author":"Topol","year":"1985","journal-title":"N Engl J Med"},{"issue":"8","key":"10.1016\/j.cardfail.2026.09.029_bib0004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0201836","article-title":"High-sensitivity C-reactive protein in heart failure with preserved ejection fraction","volume":"13","author":"DuBrock","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0005","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.jchf.2023.06.031","article-title":"Interleukin-6 in patients with heart failure and preserved ejection fraction","volume":"11","author":"Alogna","year":"2023","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0006","doi-asserted-by":"crossref","DOI":"10.1016\/j.jchf.2025.102638","article-title":"What causes inflammation in heart failure and preserved ejection fraction? Potential role of eicosanoid adipokines","author":"Packer","year":"2025","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0007","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00392-011-0305-4","article-title":"Contribution of comorbidities to functional impairment is higher in heart failure with preserved than with reduced ejection fraction","volume":"100","author":"Edelmann","year":"2011","journal-title":"Clin Res Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0008","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.jacc.2011.11.040","article-title":"Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction","volume":"59","author":"Ather","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0009","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1001\/jama.300.4.431","article-title":"Heart failure with preserved ejection fraction: treat now by treating comorbidities","volume":"300","author":"Shah","year":"2008","journal-title":"JAMA"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0010","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":"10.1016\/j.cardfail.2026.09.029_bib0011","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1093\/cvr\/cvy038","article-title":"Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening","volume":"114","author":"Sorop","year":"2018","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0012","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1161\/CIRCULATIONAHA.120.045810","article-title":"Proteomic evaluation of the comorbidity-inflammation paradigm in heart failure with preserved ejection fraction: results from the PROMIS-HFpEF study","volume":"142","author":"Sanders-van Wijk","year":"2020","journal-title":"Circulation"},{"issue":"4","key":"10.1016\/j.cardfail.2026.09.029_bib0013","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.116.003989","article-title":"Biomarker profiles in heart failure patients with preserved and reduced ejection fraction","volume":"6","author":"Tromp","year":"2017","journal-title":"J Am Heart Assoc"},{"issue":"11","key":"10.1016\/j.cardfail.2026.09.029_bib0014","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.018549","article-title":"Interleukin 6 and development of heart failure with preserved ejection fraction in the general population","volume":"10","author":"Chia","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0015","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.amjcard.2021.11.045","article-title":"Inflammatory markers and risk of heart failure with reduced to preserved ejection fraction","volume":"167","author":"Albar","year":"2022","journal-title":"Am J Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0016","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.jacc.2009.12.045","article-title":"Health ABC Study Investigators. Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) Study","volume":"55","author":"Kalogeropoulos","year":"2010","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"10.1016\/j.cardfail.2026.09.029_bib0017","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.122.010051","article-title":"Adverse outcomes associated with interleukin-6 in patients recently hospitalized for heart failure with preserved ejection fraction","volume":"16","author":"Mooney","year":"2023","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0018","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1093\/eurheartj\/ehy531","article-title":"Prevalence and correlates of coronary microvascular dysfunction in heart failure and preserved ejection fraction: PROMIS-HFpEF","volume":"39","author":"Shah","year":"2018","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0019","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1093\/eurheartj\/ehab653","article-title":"Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction","volume":"42","author":"Sinha","year":"2021","journal-title":"Eur Heart J"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0020","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12968-021-00807-3","article-title":"Cardiovascular magnetic resonance assessment of coronary flow reserve improves risk stratification in heart failure with preserved ejection fraction","volume":"23","author":"Kato","year":"2021","journal-title":"J Cardiovasc Magn Reson"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0021","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijcard.2025.133064","article-title":"The association of coronary microvascular dysfunction and cardiac maladaptation with clinical outcomes in heart failure with preserved ejection fraction: A prospective dynamic SPECT study","volume":"425","author":"Hung","year":"2025","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0022","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1161\/CIRCRESAHA.108.184408","article-title":"Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs","volume":"104","author":"Kr\u00fcger","year":"2009","journal-title":"Circ Res"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0023","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1161\/CIRCULATIONAHA.114.013215","article-title":"Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin","volume":"131","author":"Zile","year":"2015","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0024","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1161\/CIRCULATIONAHA.111.076075","article-title":"Low myocardial protein kinase G activity in heart failure with preserved ejection fraction","volume":"126","author":"van Heerebeek","year":"2012","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0025","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/cvr\/cvs353","article-title":"Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fraction","volume":"97","author":"Hamdani","year":"2013","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0026","doi-asserted-by":"crossref","first-page":"32831","DOI":"10.1074\/jbc.M603416200","article-title":"cGMP-dependent protein kinase type I inhibits TAB1-p38 mitogen-activated protein kinase apoptosis signaling in cardiac myocytes","volume":"281","author":"Fiedler","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0027","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1161\/CIRCULATIONAHA.110.971853","article-title":"Omega-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cyclic GMP\/protein kinase G signaling in cardiac fibroblasts","volume":"123","author":"Chen","year":"2011","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0028","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1161\/CIRCRESAHA.121.318159","article-title":"From systemic inflammation to myocardial fibrosis: the heart failure with preserved ejection fraction paradigm revisited","volume":"128","author":"Paulus","year":"2021","journal-title":"Circ Res"},{"issue":"12","key":"10.1016\/j.cardfail.2026.09.029_bib0029","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1161\/CIRCRESAHA.116.308688","article-title":"Deletion of interleukin-6 attenuates pressure overload-induced left ventricular hypertrophy and dysfunction","volume":"118","author":"Zhao","year":"2016","journal-title":"Circ Res"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0030","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1161\/HYPERTENSIONAHA.109.148635","article-title":"Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats","volume":"56","author":"Mel\u00e9ndez","year":"2010","journal-title":"Hypertension"},{"issue":"6","key":"10.1016\/j.cardfail.2026.09.029_bib0031","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.3390\/jcm15062279","article-title":"Association of inflammatory-hematological biomarkers with hypertension and related comorbidities","volume":"15","author":"Gosav","year":"2026","journal-title":"J Clin Med"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0032","doi-asserted-by":"crossref","DOI":"10.1155\/mi\/8912366","article-title":"Integrative inflammation-metabolism indicator for cardiovascular-kidney-metabolic syndrome: evaluating the C-reactive protein-triglyceride glucose index for risk stratification and progression across three national cohorts","volume":"2026","author":"Zeng","year":"2026","journal-title":"Mediators Inflamm"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0033","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1161\/01.HYP.0000226046.58883.32","article-title":"Val-MARC Investigators. Valsartan, blood pressure reduction, and C-reactive protein: primary report of the Val-MARC trial","volume":"48","author":"Ridker","year":"2006","journal-title":"Hypertension"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0034","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1001\/jama.2009.1347","article-title":"Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial","volume":"302","author":"Pradhan","year":"2009","journal-title":"JAMA"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0035","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.2337\/db23-0171","article-title":"IL-6 trans-signaling is increased in diabetes, impacted by glucolipotoxicity, and associated with liver stiffness and fibrosis in fatty liver disease","volume":"72","author":"Gunes","year":"2023","journal-title":"Diabetes"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0036","doi-asserted-by":"crossref","first-page":"9002","DOI":"10.1111\/dom.71106","article-title":"Effects of GLP-1 receptor agonists and dual GIP\/GLP-1 receptor agonists on inflammatory and metabolic biomarkers in type 2 diabetes: a systematic review and meta-analysis","volume":"28","author":"Kanbay","year":"2026","journal-title":"Diabetes Obes Metab"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0037","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1111\/dom.15586","article-title":"The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials","volume":"26","author":"Buttice","year":"2024","journal-title":"Diabetes Obes Metab"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0038","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1186\/s12933-025-03014-x","article-title":"FIVE-STAR Investigators. Effects of finerenone on arterial stiffness and cardiorenal biomarkers in patients with type 2 diabetes and chronic kidney disease: a randomised placebo-controlled mechanistic trial (FIVE-STAR)","volume":"24","author":"Tanaka","year":"2025","journal-title":"Cardiovasc Diabetol"},{"issue":"25","key":"10.1016\/j.cardfail.2026.09.029_bib0039","article-title":"Central adiposity or hypertension: which drives heart failure with a preserved ejection fraction?","volume":"S0735-1097","author":"Packer","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"25","key":"10.1016\/j.cardfail.2026.09.029_bib0040","first-page":"07341","article-title":"Is type 2 diabetes a modifiable risk factor for the evolution and progression of heart failure with a preserved ejection fraction?","volume":"S0735-1097","author":"Packer","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"25","key":"10.1016\/j.cardfail.2026.09.029_bib0041","article-title":"Chronic kidney disease in patients with heart failure with a preserved ejection fraction: the underlying role of visceral adiposity","volume":"S0735-1097","author":"Packer","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0042","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.jacc.2025.06.055","article-title":"The adipokine hypothesis of heart failure with a preserved ejection fraction: a novel framework to explain pathogenesis and guide treatment","volume":"86","author":"Packer","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0043","doi-asserted-by":"crossref","first-page":"7753","DOI":"10.1038\/s41467-022-35323-0","article-title":"Genetic architecture of heart failure with preserved versus reduced ejection fraction","volume":"13","author":"Joseph","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0044","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41588-024-02064-3","article-title":"Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes","volume":"57","author":"Henry","year":"2025","journal-title":"Nat Genet"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0045","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12933-025-02738-0","article-title":"Circulating mediators linking cardiometabolic diseases to HFpEF: a mediation Mendelian randomization analysis","volume":"24","author":"Lin","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0046","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.cardfail.2011.03.010","article-title":"The impact of extra cardiac comorbidities on pressure volume relations in heart failure and preserved ejection fraction","volume":"17","author":"Abramov","year":"2011","journal-title":"J Card Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0047","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1056\/NEJMoa0805450","article-title":"I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction","volume":"359","author":"Massie","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0048","doi-asserted-by":"crossref","first-page":"3741","DOI":"10.1093\/eurheartj\/ehab499","article-title":"Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction","volume":"42","author":"Jackson","year":"2021","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0049","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/j.jacc.2020.02.009","article-title":"Systolic blood pressure in heart failure with preserved ejection fraction treated with sacubitril\/valsartan","volume":"75","author":"Selvaraj","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0050","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/ejhf.1060","article-title":"Systolic blood pressure and cardiovascular outcomes in heart failure with preserved ejection fraction: an analysis of the TOPCAT trial","volume":"20","author":"Selvaraj","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0051","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/ajh\/hpx210","article-title":"Spironolactone and resistant hypertension in heart failure with preserved ejection fraction","volume":"31","author":"Rossignol","year":"2018","journal-title":"Am J Hypertens"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0052","first-page":"1304","article-title":"Empagliflozin in resistant hypertension and heart failure with preserved ejection fraction: the EMPEROR-Preserved trial","volume":"46","author":"B\u00f6hm","year":"2025","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0053","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1093\/eurheartj\/ehac693","article-title":"irrespective of blood pressure, improves outcomes in heart failure with preserved ejection fraction: the EMPEROR-Preserved trial","volume":"44","author":"B\u00f6hm","year":"2023","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0054","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1056\/NEJMoa1307684","article-title":"SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus","volume":"369","author":"Scirica","year":"2013","journal-title":"N Engl J Med."},{"key":"10.1016\/j.cardfail.2026.09.029_bib0055","doi-asserted-by":"crossref","first-page":"e294","DOI":"10.1161\/CIR.0000000000000691","volume":"140","author":"Dunlay","year":"2019","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0056","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0140-6736(22)01429-5","article-title":"SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials","volume":"400","author":"Vaduganathan","year":"2022","journal-title":"Lancet"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0057","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1161\/CIRCULATIONAHA.122.059785","article-title":"EMPEROR-Preserved Trial Committees and Investigators. Empagliflozin for heart failure with preserved left ventricular ejection fraction with and without diabetes","volume":"146","author":"Filippatos","year":"2022","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0058","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.jacc.2025.06.058","article-title":"SUMMIT Trial Study Group. Influence of type 2 diabetes on the effects of tirzepatide in patients with heart failure and a preserved ejection fraction with obesity: a prespecified stratification-based analysis","volume":"86","author":"Packer","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0059","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1056\/NEJMoa1306033","article-title":"BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease","volume":"369","author":"de Zeeuw","year":"2013","journal-title":"N Engl J Med."},{"key":"10.1016\/j.cardfail.2026.09.029_bib0060","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1056\/NEJMoa065485","article-title":"Correction of anemia with epoetin alfa in chronic kidney disease","volume":"355","author":"Singh","year":"2006","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0061","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1681\/ASN.0000000000000321","article-title":"Daprodustat and heart failure in CKD","volume":"35","author":"Cunningham","year":"2024","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0062","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1016\/j.jacc.2024.08.028","article-title":"STEP-HFpEF Trial Committees and Investigators. Inflammation in obesity-related HFpEF: The STEP-HFpEF program","volume":"84","author":"Verma","year":"2024","journal-title":"J Am Coll Cardiol"},{"issue":"26","key":"10.1016\/j.cardfail.2026.09.029_bib0063","article-title":"Management of heart failure with preserved ejection fraction: 2026 ACC Expert Consensus Decision Pathway: A Report of the American College of Cardiology Solution Set Oversight Committee","volume":"S0735-1097","author":"Kittleson","year":"2026","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0064","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/S0735-1097(03)00992-6","article-title":"Effect of tumor necrosis factor-alpha on endothelial and inducible nitric oxide synthase messenger ribonucleic acid expression and nitric oxide synthesis in ischemic and nonischemic isolated rat heart","volume":"42","author":"Paz","year":"2003","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0065","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.yjmcc.2005.11.010","article-title":"Activation of JNK and xanthine oxidase by TNF-alpha impairs nitric oxide-mediated dilation of coronary arterioles","volume":"40","author":"Zhang","year":"2006","journal-title":"J Mol Cell Cardiol"},{"issue":"11","key":"10.1016\/j.cardfail.2026.09.029_bib0066","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0187189","article-title":"Interaction of IL-6 and TNF-alpha contributes to endothelial dysfunction in type 2 diabetic mouse hearts","volume":"12","author":"Lee","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0067","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ahj.2017.02.035","article-title":"High-sensitivity C-reactive protein is an independent marker of abnormal coronary vasoreactivity in patients with non-obstructive coronary artery disease","volume":"190","author":"Sara","year":"2017","journal-title":"Am Heart J"},{"issue":"6","key":"10.1016\/j.cardfail.2026.09.029_bib0068","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.jcmg.2012.12.011","article-title":"Inflammation and microvascular dysfunction in cardiac syndrome X patients without conventional risk factors for coronary artery disease","volume":"6","author":"Recio-Mayoral","year":"2013","journal-title":"JACC Cardiovasc Imaging"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0069","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.atherosclerosis.2016.05.036","article-title":"Treatment with tumor necrosis factor inhibitors restores coronary microvascular function in young patients with severe psoriasis","volume":"251","author":"Piaserico","year":"2016","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0070","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1161\/CIRCULATIONAHA.107.731877","article-title":"Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis","volume":"117","author":"Ikonomidis","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0071","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1136\/heartjnl-2016-310875","article-title":"Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction","volume":"103","author":"Holte","year":"2017","journal-title":"Heart"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0072","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/ejhf.1671","article-title":"Endothelium-dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction","volume":"22","author":"Yang","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0073","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/ejhf.2435","article-title":"Sex differences in proteomic correlates of coronary microvascular dysfunction among patients with heart failure and preserved ejection fraction","volume":"24","author":"Chandramouli","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0074","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1161\/CIRCHEARTFAILURE.109.931451","article-title":"Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction","volume":"4","author":"Westermann","year":"2011","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0075","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.jchf.2020.04.007","article-title":"Endomyocardial biopsy characterization of heart failure with preserved ejection fraction and prevalence of cardiac amyloidosis","volume":"8","author":"Hahn","year":"2020","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0076","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jchf.2015.10.007","article-title":"Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction","volume":"4","author":"Franssen","year":"2016","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0077","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1172\/JCI118074","article-title":"Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines","volume":"96","author":"De Caterina","year":"1995","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0078","doi-asserted-by":"crossref","first-page":"9114","DOI":"10.1073\/pnas.93.17.9114","article-title":"Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells","volume":"93","author":"Khan","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0079","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1161\/01.CIR.97.21.2123","article-title":"Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans","volume":"97","author":"Lerman","year":"1998","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0080","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.yjmcc.2019.10.005","article-title":"Diastolic dysfunction is initiated by cardiomyocyte impairment ahead of endothelial dysfunction due to increased oxidative stress and inflammation in an experimental prediabetes model","volume":"137","author":"Waddingham","year":"2019","journal-title":"J Mol Cell Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0081","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.jacc.2005.10.050","article-title":"Relevance of coronary microvascular flow impairment to long-term remodeling and systolic dysfunction in hypertrophic cardiomyopathy","volume":"47","author":"Olivotto","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0082","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2174\/157016108785909779","article-title":"The cardiac microvasculature in hypertension, cardiac hypertrophy and diastolic heart failure","volume":"6","author":"Hoenig","year":"2008","journal-title":"Curr Vasc Pharmacol"},{"issue":"2","key":"10.1016\/j.cardfail.2026.09.029_bib0083","doi-asserted-by":"crossref","DOI":"10.1136\/openhrt-2025-003509","article-title":"Prevalence and importance of coronary microvascular dysfunction in patients with heart failure and reduced or mildly reduced ejection fraction","volume":"12","author":"Nordberg Backelin","year":"2025","journal-title":"Open Heart"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0084","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/ehf2.14626","article-title":"Impact of coronary microvascular dysfunction in heart failure with preserved ejection fraction: a meta-analysis","volume":"11","author":"D'Amario","year":"2024","journal-title":"ESC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0085","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/ejhf.2010","article-title":"Coronary microvascular dysfunction is associated with exertional haemodynamic abnormalities in patients with heart failure with preserved ejection fraction","volume":"23","author":"Ahmad","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0086","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/ehf2.14929","article-title":"Coronary microvascular dysfunction and left heart filling pressures in patients with type 2 diabetes","volume":"11","author":"Wolsk","year":"2024","journal-title":"ESC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0087","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41586-019-1100-z","article-title":"Nitrosative stress drives heart failure with preserved ejection fraction","volume":"568","author":"Schiattarella","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0088","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nature14332","article-title":"Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease","volume":"519","author":"Lee","year":"2015","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.cardfail.2026.09.029_bib0089","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.96006","article-title":"Nitric oxide-sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction","volume":"3","author":"Wilck","year":"2018","journal-title":"JCI Insight"},{"issue":"8","key":"10.1016\/j.cardfail.2026.09.029_bib0090","doi-asserted-by":"crossref","DOI":"10.1111\/micc.12888","article-title":"PDE9A inhibition improves coronary microvascular rarefaction and left ventricular diastolic dysfunction in the ZSF1 rat model of HFpEF","volume":"31","author":"Fopiano","year":"2024","journal-title":"Microcirculation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0091","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3389\/fphys.2020.00345","article-title":"Enhanced cardiomyocyte function in hypertensive rats with diastolic dysfunction and human heart failure patients after acute treatment with soluble guanylyl cyclase (sGC) activator","volume":"11","author":"Kolijn","year":"2020","journal-title":"Front Physiol"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0092","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41467-017-02483-3","article-title":"Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes","volume":"9","author":"Krysiak","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0093","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1161\/01.CIR.99.16.2113","article-title":"Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure","volume":"99","author":"Katz","year":"1999","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0094","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1161\/CIRCRESAHA.114.301475","article-title":"Nitrite therapy improves left ventricular function during heart failure via restoration of nitric oxide-mediated cytoprotective signaling","volume":"114","author":"Bhushan","year":"2014","journal-title":"Circ Res"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0095","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1161\/CIRCRESAHA.108.193326","article-title":"Hypophosphorylation of the stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium","volume":"104","author":"Borb\u00e9ly","year":"2009","journal-title":"Circ Res"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0096","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1001\/jama.2018.14852","article-title":"National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network. Effect of inorganic nitrite vs placebo on exercise capacity among patients with heart failure with preserved ejection fraction: The INDIE-HFpEF randomized clinical trial","volume":"320","author":"Borlaug","year":"2018","journal-title":"JAMA"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0097","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1056\/NEJMoa1510774","article-title":"NHLBI Heart Failure Clinical Research Network. Isosorbide mononitrate in heart failure with preserved ejection fraction","volume":"373","author":"Redfield","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0098","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.mayocp.2023.08.031","article-title":"Inorganic nitrite to amplify the benefits and tolerability of exercise training in heart failure with preserved ejection fraction: the INABLE-Training trial","volume":"99","author":"Borlaug","year":"2024","journal-title":"Mayo Clin Proc"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0099","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1001\/jama.2020.15922","article-title":"VITALITY-HFpEF Study Group. Effect of vericiguat vs placebo on quality of life in patients with heart failure and preserved ejection fraction: The VITALITY-HFpEF Randomized Clinical Trial","volume":"324","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0100","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1001\/jama.2020.16641","article-title":"Effect of praliciguat on peak rate of oxygen consumption in patients with heart failure with preserved ejection fraction: the CAPACITY HFpEF randomized clinical trial","volume":"324","author":"Udelson","year":"2020","journal-title":"JAMA"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0101","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1001\/jama.2013.2024","article-title":"RELAX Trial. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial","volume":"309","author":"Redfield","year":"2013","journal-title":"JAMA"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0102","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/eurheartj\/ehw593","article-title":"Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED EF (SOCRATES-PRESERVED) study","volume":"38","author":"Pieske","year":"2017","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0103","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1161\/CIRCULATIONAHA.124.069340","article-title":"Tadalafil for treatment of combined postcapillary and precapillary pulmonary hypertension in patients with heart failure and preserved ejection fraction: a randomized controlled phase 3 study","volume":"150","author":"Hoeper","year":"2024","journal-title":"Circulation"},{"issue":"8","key":"10.1016\/j.cardfail.2026.09.029_bib0104","doi-asserted-by":"crossref","DOI":"10.1016\/j.jchf.2026.103057","article-title":"Genetically proxied interleukin-6 signaling inhibition and heart failure risk","volume":"14","author":"Zangas","year":"2026","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0105","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.jacc.2019.12.069","article-title":"Multiple plasma biomarkers for risk stratification in patients with heart failure and preserved ejection fraction","volume":"75","author":"Chirinos","year":"2020","journal-title":"J Am Coll Cardiol"},{"issue":"6","key":"10.1016\/j.cardfail.2026.09.029_bib0106","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0099495","article-title":"Alberta HEART Investigators. Circulating levels of tumor necrosis factor-alpha receptor 2 are increased in heart failure with preserved ejection fraction relative to heart failure with reduced ejection fraction: evidence for a divergence in pathophysiology","volume":"9","author":"Putko","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0107","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ijcard.2007.05.061","article-title":"Inflammatory pathways in patients with heart failure and preserved ejection fraction","volume":"129","author":"Niethammer","year":"2008","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0108","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.jacc.2018.06.050","article-title":"Identifying pathophysiological mechanisms in heart failure with reduced versus preserved ejection fraction","volume":"72","author":"Tromp","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0109","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.amjcard.2021.11.045","article-title":"Inflammatory markers and risk of heart failure with reduced to preserved ejection fraction","volume":"167","author":"Albar","year":"2022","journal-title":"Am J Cardiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0110","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/ejhf.1482","article-title":"The clinical significance of interleukin-6 in heart failure: results from the BIOSTAT-CHF study","volume":"21","author":"Markousis-Mavrogenis","year":"2019","journal-title":"Eur J Heart Fail"},{"issue":"2","key":"10.1016\/j.cardfail.2026.09.029_bib0111","doi-asserted-by":"crossref","DOI":"10.1002\/clc.24181","article-title":"Association between omentin-1 and heart failure with preserved ejection fraction in Chinese elderly patients","volume":"47","author":"Su","year":"2023","journal-title":"Clin Cardiol"},{"issue":"2","key":"10.1016\/j.cardfail.2026.09.029_bib0112","doi-asserted-by":"crossref","DOI":"10.1016\/j.jchf.2025.102712","article-title":"Prevalence and associations of systemic inflammation in heart failure across the spectrum of ejection fraction","volume":"14","author":"Borlaug","year":"2026","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0113","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1161\/HYPERTENSIONAHA.109.148635","article-title":"Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats","volume":"56","author":"Mel\u00e9ndez","year":"2010","journal-title":"Hypertension"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0114","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1161\/HYPERTENSIONAHA.110.158915","article-title":"C-reactive protein overexpression exacerbates pressure overload-induced cardiac remodeling through enhanced inflammatory response","volume":"57","author":"Nagai","year":"2011","journal-title":"Hypertension"},{"issue":"7","key":"10.1016\/j.cardfail.2026.09.029_bib0115","doi-asserted-by":"crossref","DOI":"10.1172\/JCI196238","article-title":"PPARalpha-NF-kappaB heterodimer mediates obesity-induced diastolic dysfunction through autocrine production of IL-6","volume":"136","author":"Oka","year":"2026","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0116","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.bbrc.2017.10.119","article-title":"Interleukin-6 deficiency attenuates angiotensin II-induced cardiac pathogenesis with increased myocyte hypertrophy","volume":"494","author":"Chen","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0117","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1161\/CIRCRESAHA.116.308688","article-title":"Deletion of interleukin-6 attenuates pressure overload-induced left ventricular hypertrophy and dysfunction","volume":"118","author":"Zhao","year":"2016","journal-title":"Circ Res"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0118","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13075-025-03700-x","article-title":"Interleukin-6 blockade modulates monocyte recruitment to protect against diastolic dysfunction associated with inflammatory arthritis","volume":"28","author":"Christoforou","year":"2026","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0119","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.3899\/jrheum.131540","article-title":"Tocilizumab treatment increases left ventricular ejection fraction and decreases left ventricular mass index in patients with rheumatoid arthritis without cardiac symptoms: assessed using 3.0 Tesla cardiac magnetic resonance imaging","volume":"41","author":"Kobayashi","year":"2014","journal-title":"J Rheumatol"},{"issue":"6","key":"10.1016\/j.cardfail.2026.09.029_bib0120","doi-asserted-by":"crossref","first-page":"F654","DOI":"10.1152\/ajprenal.00396.2021","article-title":"Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice","volume":"323","author":"Tanaka","year":"2022","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0121","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1093\/cvr\/cvy013","article-title":"TAIPAI Study Group. IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis","volume":"114","author":"Chou","year":"2018","journal-title":"Cardiovasc Res"},{"issue":"2","key":"10.1016\/j.cardfail.2026.09.029_bib0122","doi-asserted-by":"crossref","first-page":"R590","DOI":"10.1152\/ajpregu.00207.2009","article-title":"Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells","volume":"299","author":"Li","year":"2010","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0123","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1161\/CIRCULATIONAHA.106.643585","article-title":"Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state","volume":"115","author":"Sun","year":"2007","journal-title":"Circulation"},{"issue":"14","key":"10.1016\/j.cardfail.2026.09.029_bib0124","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.122.029668","article-title":"Interleukin-1beta disruption protects male mice from heart failure with preserved ejection fraction pathogenesis","volume":"12","author":"Srinivas","year":"2023","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0125","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jacbts.2022.08.003","article-title":"Inflammatory macrophage interleukin-1\u03b2 mediates high-fat diet-induced heart failure with preserved ejection fraction","volume":"8","author":"Liu","year":"2022","journal-title":"JACC Basic Transl Sci"},{"issue":"6","key":"10.1016\/j.cardfail.2026.09.029_bib0126","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.113.000267","article-title":"Toll-like receptor-2 mediates adaptive cardiac hypertrophy in response to pressure overload through interleukin-1beta upregulation via nuclear factor kappaB activation","volume":"2","author":"Higashikuni","year":"2013","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0127","doi-asserted-by":"crossref","first-page":"23115","DOI":"10.1074\/jbc.M100814200","article-title":"gp130 plays a critical role in pressure overload-induced cardiac hypertrophy","volume":"276","author":"Uozumi","year":"2001","journal-title":"J Biol Chem"},{"issue":"12","key":"10.1016\/j.cardfail.2026.09.029_bib0128","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000967","article-title":"Transmembrane tumor necrosis factor alpha attenuates pressure-overload cardiac hypertrophy via tumor necrosis factor receptor 2","volume":"18","author":"Miao","year":"2020","journal-title":"PLoS Biol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0129","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.2337\/diabetes.52.5.1104","article-title":"Adipose tissue is a major source of interleukin-1 receptor antagonist: upregulation in obesity and inflammation","volume":"52","author":"Juge-Aubry","year":"2003","journal-title":"Diabetes"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0130","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1210\/jcem.87.3.8351","article-title":"IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin?","volume":"87","author":"Meier","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0131","first-page":"CR180","article-title":"Association between toll-like receptor polymorphisms and serum levels of tumor necrosis factor-alpha and its soluble receptors in obese children","volume":"16","author":"Jermendy","year":"2010","journal-title":"Med Sci Monit"},{"issue":"7","key":"10.1016\/j.cardfail.2026.09.029_bib0132","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0133494","article-title":"Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation","volume":"10","author":"Sindhu","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0133","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41577-023-00856-y","article-title":"Targeting IL-6 trans-signalling: past, present and future prospects","volume":"23","author":"Rose-John","year":"2023","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0134","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-65667-0","article-title":"Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum","volume":"14","author":"Andrzejczyk","year":"2024","journal-title":"Sci Rep"},{"issue":"1","key":"10.1016\/j.cardfail.2026.09.029_bib0135","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-24226-1","article-title":"Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events","volume":"12","author":"Regan","year":"2022","journal-title":"Sci Rep"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0136","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1161\/CIRCHEARTFAILURE.113.000344","article-title":"Health ABC Study. Soluble tumor necrosis factor receptors and heart failure risk in older adults: Health, Aging, and Body Composition (Health ABC) Study","volume":"7","author":"Marti","year":"2014","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0137","doi-asserted-by":"crossref","first-page":"34","DOI":"10.18087\/cardio.2024.3.n2534","article-title":"Interleukin 6 signalling in heart failure with preserved and reduced ejection fraction","volume":"64","author":"Samoilova","year":"2024","journal-title":"Kardiologiia"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0138","doi-asserted-by":"crossref","first-page":"67","DOI":"10.18087\/cardio.2025.11.n2995","article-title":"Interleukin-1 signalling inhibitors in heart failure with preserved and reduced ejection fraction","volume":"65","author":"Samoilova","year":"2025","journal-title":"Kardiologiia"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0139","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1161\/ATVBAHA.111.229435","article-title":"Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice","volume":"32","author":"Schuett","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0140","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1161\/01.CIR.0000124490.27666.B2","article-title":"Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)","volume":"109","author":"Mann","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0141","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1161\/01.CIR.0000077913.60364.D2","volume":"107","author":"Chung","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0142","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1161\/CIRCULATIONAHA.118.038010","article-title":"Anti-inflammatory therapy with canakinumab for the prevention of hospitalization for heart failure","volume":"139","author":"Everett","year":"2019","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0143","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1161\/CIRCULATIONAHA.120.050498","article-title":"Myocardial gene expression signatures in human heart failure with preserved ejection fraction","volume":"143","author":"Hahn","year":"2021","journal-title":"Circulation"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0144","first-page":"847","article-title":"Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid","volume":"83","author":"Fried","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0145","first-page":"4196","article-title":"Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo","volume":"82","author":"Mohamed-Ali","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0146","doi-asserted-by":"crossref","DOI":"10.1155\/2010\/513948","article-title":"Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: a review","volume":"2010","author":"Fain","year":"2010","journal-title":"Mediators Inflamm"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0147","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrrheum.2014.127","article-title":"IL-6 biology: implications for clinical targeting in rheumatic disease","volume":"10","author":"Calabrese","year":"2014","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"10.1016\/j.cardfail.2026.09.029_bib0148","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cyto.2010.06.013","article-title":"Impaired hepatic removal of interleukin-6 in patients with liver cirrhosis","volume":"53","author":"Wiest","year":"2011","journal-title":"Cytokine"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0149","doi-asserted-by":"crossref","first-page":"E597","DOI":"10.1152\/ajpendo.00206.2019","article-title":"Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice","volume":"317","author":"Whitham","year":"2019","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0150","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1093\/eurheartj\/ehag029","article-title":"Causal role of adipose tissue-derived adipokines in the pathogenesis of heart failure with preserved ejection fraction: experimental demonstration as the basis for clinical targeting","volume":"47","author":"Packer","year":"2026","journal-title":"Eur Heart J"},{"issue":"2","key":"10.1016\/j.cardfail.2026.09.029_bib0151","doi-asserted-by":"crossref","DOI":"10.1016\/j.jchf.2025.102822","article-title":"Evolutionary history of the comorbidity-driven coronary microvascular endothelial inflammation hypothesis and its metamorphosis to the adipokine hypothesis of heart failure with a preserved ejection fraction","volume":"14","author":"Packer","year":"2026","journal-title":"JACC Heart Fail"},{"issue":"8","key":"10.1016\/j.cardfail.2026.09.029_bib0152","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.118.005036","article-title":"IL-1 blockade in patients with heart failure with preserved ejection fraction","volume":"11","author":"Van Tassell","year":"2018","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0153","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/art.41095","article-title":"Cardiovascular safety of tocilizumab versus etanercept in rheumatoid arthritis: a randomized controlled trial","volume":"72","author":"Giles","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0154","unstructured":"Sylvant (siltuximab): Package Insert\/Prescribing Information. Available at: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/125496s013lbl.pdf."},{"key":"10.1016\/j.cardfail.2026.09.029_bib0155","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1093\/eurheartj\/ehae538","article-title":"Colchicine in acutely decompensated heart failure: the COLICA trial","volume":"45","author":"Pascual-Figal","year":"2024","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0156","unstructured":"Reversing microvascular dysfunction in heart failure with preserved ejection fraction (COL-Micro-HF). ClinicalTrials.gov ID NCT06217120"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0157","unstructured":"Colchicine in HFpEF (COLpEF). ClinicalTrials.gov ID NCT04857931"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0158","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.mayocp.2025.02.022","article-title":"Acute effects of myeloperoxidase inhibition on exercise hemodynamics in heart failure with preserved ejection fraction: a randomized clinical trial","volume":"100","author":"Popovic","year":"2025","journal-title":"Mayo Clin Proc"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0159","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cardfail.2023.04.003","article-title":"Myeloperoxidase inhibition in heart failure with preserved or mildly reduced ejection fraction: SATELLITE trial results","volume":"30","author":"Lam","year":"2024","journal-title":"J Card Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0160","doi-asserted-by":"crossref","DOI":"10.1038\/s41591-026-04615-z","article-title":"Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial","author":"Lund","year":"2026","journal-title":"Nat Med"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0161","first-page":"xuag153","article-title":"Ziltivekimab in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the ATHENA and HERMES trials","author":"Mendieta","year":"2026","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.cardfail.2026.09.029_bib0162","unstructured":"Joseph A. Novo Nordisk stops two cardiovascular trials of drug aimed at lowering inflammation. STAT News. Available at: https:\/\/www.statnews.com\/2026\/09\/07\/novo-nordisk-heart-studies-inflammation-ziltivekimab\/."}],"container-title":["Journal of Cardiac Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1071916426005944?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1071916426005944?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:45:06Z","timestamp":1793364306000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1071916426005944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":162,"alternative-id":["S1071916426005944"],"URL":"https:\/\/doi.org\/10.1016\/j.cardfail.2026.09.029","relation":{},"ISSN":["1071-9164"],"issn-type":[{"value":"1071-9164","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The Comorbidity-Driven Interleukin-6-Mediated Systemic Inflammation Hypothesis of Heart Failure With Preserved Ejection Fraction: A Decade of Testing Ends in Disappointment","name":"articletitle","label":"Article Title"},{"value":"Journal of Cardiac Failure","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cardfail.2026.09.029","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}