{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:34:56Z","timestamp":1793061296688,"version":"4.5.0"},"reference-count":39,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T00:00:00Z","timestamp":1742688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JACC: Heart Failure"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.jchf.2025.03.002","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T14:17:53Z","timestamp":1743430673000},"page":"102435","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1016","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8418-7623","authenticated-orcid":false,"given":"Senthil","family":"Selvaraj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoneta","family":"Karaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio A.","family":"Chirinos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Denney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabby","family":"Grosso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Fernando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishon","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Demastus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Langham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dushyant","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Maynard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Pourmussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart B.","family":"Prenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-079X","authenticated-orcid":false,"given":"Jordana B.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Ischiropoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Rickels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Poole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Church","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Wolfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3811-9491","authenticated-orcid":false,"given":"Daniel P.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Putt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8093-4465","authenticated-orcid":false,"given":"Kenneth B.","family":"Margulies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payman","family":"Zamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jchf.2025.03.002_bib1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1161\/CIRCULATIONAHA.114.012957","article-title":"Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction","volume":"131","author":"Zamani","year":"2015","journal-title":"Circulation"},{"key":"10.1016\/j.jchf.2025.03.002_bib2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jacbts.2020.01.003","article-title":"peripheral determinants of oxygen utilization in heart failure with preserved ejection fraction: central role of adiposity","volume":"5","author":"Zamani","year":"2020","journal-title":"JACC Basic Transl Sci"},{"key":"10.1016\/j.jchf.2025.03.002_bib3","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1161\/CIRCRESAHA.116.309832","article-title":"Pharmacokinetics and pharmacodynamics of inorganic nitrate in heart failure with preserved ejection fraction","volume":"120","author":"Zamani","year":"2017","journal-title":"Circ Res"},{"key":"10.1016\/j.jchf.2025.03.002_bib4","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1161\/CIRCULATIONAHA.117.029058","article-title":"Exercise intolerance in heart failure with preserved ejection fraction: diagnosing and ranking its causes using personalized O(2) pathway analysis","volume":"137","author":"Houstis","year":"2018","journal-title":"Circulation"},{"key":"10.1016\/j.jchf.2025.03.002_bib5","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1161\/CIRCULATIONAHA.121.054858","article-title":"Energetic basis for exercise-induced pulmonary congestion in heart failure with preserved ejection fraction","volume":"144","author":"Burrage","year":"2021","journal-title":"Circulation"},{"key":"10.1016\/j.jchf.2025.03.002_bib6","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1093\/eurheartj\/ehz713","article-title":"The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction","volume":"40","author":"Reddy","year":"2019","journal-title":"Eur Heart J"},{"key":"10.1016\/j.jchf.2025.03.002_bib7","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/j.jacc.2021.08.073","article-title":"Effect of beta-Blocker withdrawal on functional capacity in heart failure and preserved ejection fraction","volume":"78","author":"Palau","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib8","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/ejhf.1643","article-title":"Left atrial function in heart failure with preserved ejection fraction: a systematic review and meta-analysis","volume":"22","author":"Khan","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.jchf.2025.03.002_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijcard.2023.131553","article-title":"Contribution of reduced skeletal muscle perfusion reserve to exercise intolerance in heart failure with preserved ejection fraction","volume":"395","author":"Serafin","year":"2024","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib10","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.117.004129","article-title":"Fatigability, exercise intolerance, and abnormal skeletal muscle energetics in heart failure","volume":"10","author":"Weiss","year":"2017","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.jchf.2025.03.002_bib11","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1002\/ehf2.13329","article-title":"Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism","volume":"8","author":"Zamani","year":"2021","journal-title":"ESC Heart Fail"},{"key":"10.1016\/j.jchf.2025.03.002_bib12","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.cardfail.2021.02.011","article-title":"Exercise intolerance in heart failure with preserved ejection fraction: arterial stiffness and abnormal left ventricular hemodynamic responses during exercise","volume":"27","author":"Zern","year":"2021","journal-title":"J Card Fail"},{"key":"10.1016\/j.jchf.2025.03.002_bib13","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1161\/CIRCULATIONAHA.119.045033","article-title":"Implications of altered ketone metabolism and therapeutic ketosis in heart failure","volume":"141","author":"Selvaraj","year":"2020","journal-title":"Circulation"},{"issue":"20","key":"10.1016\/j.jchf.2025.03.002_bib14","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1161\/CIRCULATIONAHA.124.069732","article-title":"Randomized crossover trial of 2-week ketone ester treatment in patients with type 2 diabetes and heart failure with preserved ejection fraction","volume":"150","author":"Gopalasingam","year":"2024","journal-title":"Circulation"},{"key":"10.1016\/j.jchf.2025.03.002_bib15","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1096\/fasebj.9.8.7768357","article-title":"Insulin, ketone bodies, and mitochondrial energy transduction","volume":"9","author":"Sato","year":"1995","journal-title":"FASEB J"},{"key":"10.1016\/j.jchf.2025.03.002_bib16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.plefa.2003.09.007","article-title":"The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism","volume":"70","author":"Veech","year":"2004","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"10.1016\/j.jchf.2025.03.002_bib17","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.116.005066","article-title":"Ketone body infusion with 3-hydroxybutyrate reduces myocardial glucose uptake and increases blood flow in humans: a positron emission tomography study","volume":"6","author":"Gormsen","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.jchf.2025.03.002_bib18","first-page":"770","article-title":"Comparison of exogenous ketone administration versus dietary carbohydrate restriction on myocardial glucose suppression: a crossover clinical trial","volume":"63","author":"Selvaraj","year":"2022","journal-title":"J Nucl Med"},{"key":"10.1016\/j.jchf.2025.03.002_bib19","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1113\/JP284270","article-title":"On the interdependence of ketone body oxidation, glycogen content, glycolysis and energy metabolism in the heart","volume":"601","author":"Kadir","year":"2023","journal-title":"J Physiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib20","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1152\/jappl.1994.76.6.2253","article-title":"Balance of carbohydrate and lipid utilization during exercise: the \"crossover\" concept","volume":"76","author":"Brooks","year":"1994","journal-title":"J Appl Physiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib21","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cmet.2016.07.010","article-title":"Nutritional ketosis alters fuel preference and thereby endurance performance in athletes","volume":"24","author":"Cox","year":"2016","journal-title":"Cell Metab"},{"issue":"3","key":"10.1016\/j.jchf.2025.03.002_bib22","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jacbts.2024.10.014","article-title":"Metabolic and pharmacokinetic profiling of an exogenous ketone ester by background SGLT2 inhibitor therapy in heart failure with reduced ejection","volume":"10","author":"Selvaraj","year":"2025","journal-title":"JACC Basic Transl Sci"},{"key":"10.1016\/j.jchf.2025.03.002_bib23","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1161\/CIRCULATIONAHA.122.060402","article-title":"Metabolomic profiling of the effects of dapagliflozin in heart failure with reduced ejection fraction: DEFINE-HF","volume":"146","author":"Selvaraj","year":"2022","journal-title":"Circulation"},{"key":"10.1016\/j.jchf.2025.03.002_bib24","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.124.011980","article-title":"Metabolic effects of the SGLT2 inhibitor dapagliflozin in heart failure across the spectrum of ejection fraction","author":"Selvaraj","year":"2024","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.jchf.2025.03.002_bib25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.echo.2018.06.004","article-title":"Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: recommendations from the American Society of Echocardiography","volume":"32","author":"Mitchell","year":"2019","journal-title":"J Am Soc Echocardiogr"},{"issue":"3","key":"10.1016\/j.jchf.2025.03.002_bib26","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1001\/jamacardio.2024.4417","article-title":"Potassium nitrate in heart failure with preserved ejection fraction: a randomized clinical trial","volume":"10","author":"Zamani","year":"2025","journal-title":"JAMA Cardiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib27","first-page":"137","article-title":"Tracer priming the bicarbonate pool","volume":"45","author":"Allsop","year":"1978","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib28","article-title":"Lactate Chemical Exchange Saturation Transfer (LATEST) imaging in vivo: a biomarker for LDH activity","volume":"6","author":"DeBrosse","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.jchf.2025.03.002_bib29","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.123.029849","article-title":"Stimulation of the hydroxycarboxylic acid receptor 2 with the ketone body 3-hydroxybutyrate and niacin in patients with chronic heart failure: hemodynamic and metabolic effects","volume":"12","author":"Gopalasingam","year":"2023","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.jchf.2025.03.002_bib30","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1016\/j.jchf.2023.05.029","article-title":"Beneficial effects of ketone ester in patients with cardiogenic shock: a randomized, controlled, double-blind trial","volume":"11","author":"Berg-Hansen","year":"2023","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.jchf.2025.03.002_bib31","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1161\/CIRCULATIONAHA.123.067971","article-title":"Cardiovascular effects of oral ketone ester treatment in patients with heart failure with reduced ejection fraction: a randomized, controlled, double-blind trial","volume":"149","author":"Berg-Hansen","year":"2024","journal-title":"Circulation"},{"key":"10.1016\/j.jchf.2025.03.002_bib32","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.echo.2021.10.017","article-title":"Acute echocardiographic effects of exogenous ketone administration in healthy participants","volume":"35","author":"Selvaraj","year":"2022","journal-title":"J Am Soc Echocardiogr"},{"key":"10.1016\/j.jchf.2025.03.002_bib33","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.123.033628","article-title":"Enantiomer-specific cardiovascular effects of the ketone body 3-hydroxybutyrate","volume":"13","author":"Gopalasingam","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.jchf.2025.03.002_bib34","first-page":"1440","article-title":"Acute effects of beta-hydroxybutyrate on left ventricular function in young, healthy adults","volume":"135","author":"Oneglia","year":"2023","journal-title":"J Appl Physiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00395-023-01008-y","article-title":"Ketone body 3-hydroxybutyrate elevates cardiac output through peripheral vasorelaxation and enhanced cardiac contractility","volume":"118","author":"Homilius","year":"2023","journal-title":"Basic Res Cardiol"},{"key":"10.1016\/j.jchf.2025.03.002_bib36","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1161\/CIRCULATIONAHA.122.061828","article-title":"Challenging the hemodynamic hypothesis in heart failure with preserved ejection fraction: is exercise capacity limited by elevated pulmonary capillary wedge pressure?","volume":"147","author":"Sarma","year":"2023","journal-title":"Circulation"},{"key":"10.1016\/j.jchf.2025.03.002_bib37","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.jchf.2015.12.013","article-title":"One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction","volume":"4","author":"Eggebeen","year":"2016","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.jchf.2025.03.002_bib38","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":"10.1016\/j.jchf.2025.03.002_bib39","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.jchf.2024.02.018","article-title":"Targeted metabolomic profiling of dapagliflozin in heart failure with preserved ejection fraction: the PRESERVED-HF trial","volume":"12","author":"Selvaraj","year":"2024","journal-title":"JACC Heart Fail"}],"container-title":["JACC: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213177925002379?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213177925002379?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:21:20Z","timestamp":1793060480000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213177925002379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":39,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S2213177925002379"],"URL":"https:\/\/doi.org\/10.1016\/j.jchf.2025.03.002","relation":{},"ISSN":["2213-1779"],"issn-type":[{"value":"2213-1779","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction","name":"articletitle","label":"Article Title"},{"value":"JACC: Heart Failure","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jchf.2025.03.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.","name":"copyright","label":"Copyright"}],"article-number":"102435"}}