{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:48:22Z","timestamp":1790214502412,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"25","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/18\/50\/33807"],"award-info":[{"award-number":["FS\/18\/50\/33807"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100025409","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/SCRF\/20\/32005 and FS\/SCRF\/22\/32014"],"award-info":[{"award-number":["FS\/SCRF\/20\/32005 and FS\/SCRF\/22\/32014"]}],"id":[{"id":"10.13039\/100025409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Cardiac resynchronization therapy (CRT) produces long-term reverse remodelling which requires greater adenosine triphosphate delivery to the contractile machinery. Whilst the heart retains some metabolic flexibility in non-ischaemic cardiomyopathy, whether this correlates with reverse remodelling is unknown. This study investigated whether CRT acutely changes cardiac substrate uptake, and whether this translates to favourable reverse remodelling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The effect of CRT on cardiac substrate uptake was assessed via direct coronary flow and arteriovenous measurements, with metabolomic\/lipidomic analysis on infusions of insulin\/glucose and intralipid. Cardiac function was assessed with left ventricular pressure\u2013volume loops during implantation, and cardiac magnetic resonance before and 6 months following CRT, with and without biventricular pacing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Regardless of substrate infusion, CRT acutely improved stroke work without increasing O2 uptake on both insulin\/glucose (by 34%, P = .05) and intralipid (by 36%, P = .03). This was followed by increased fatty acid (FA) uptake on insulin\/glucose (R = 0.89, P = .03) and increased \u03b2-hydroxybutyrate uptake (R = 0.81, P = .05) during intralipid infusion. After 6 months, there was a 48% (P &amp;lt; .001) reduction in left ventricular end diastolic volume, beyond that achievable by acutely shortening or lengthening QRS duration. Reverse remodelling significantly correlated with increased FA uptake with CRT on insulin\/glucose (R = 0.71, P = .05) driven by long and medium chain uptake, and increased ketone uptake with CRT on intralipid (R = 0.79, P = .05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CRT acutely alters the metabolic phenotype of non-ischaemic cardiomyopathy towards a more physiological picture of FA uptake which correlates with reverse remodelling. Retained metabolic flexibility may therefore be critical for subsequent reverse remodelling.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaf033","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T15:06:11Z","timestamp":1740495971000},"page":"2422-2433","source":"Crossref","is-referenced-by-count":15,"title":["Metabolic flexibility and reverse remodelling of the failing human heart"],"prefix":"10.1093","volume":"46","author":[{"given":"Peregrine G","family":"Green","sequence":"first","affiliation":[{"name":"Department for Physiology, Anatomy and Genetics, University of Oxford , Oxford OX1 3PT ,","place":["UK"]},{"name":"Oxford Centre for Magnetic Resonance Research, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D","family":"Watson","sequence":"additional","affiliation":[{"name":"Oxford Centre for Magnetic Resonance Research, University of Oxford , Oxford 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