{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:11:16Z","timestamp":1789031476656,"version":"build-2803163510"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>It is unknown whether cardiac resynchronization therapy (CRT) improves systemic metabolomic profile by enhancing left ventricular function. The observational cohort study aimed to investigate the effect of CRT on left ventricular ejection fraction (LVEF) and circulating plasma metabolites in patients who had heart failure with reduced LVEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We prospectively screened patients with ischemic cardiomyopathy and nonischemic cardiomyopathy who received CRT with a defibrillator for LVEF \u226435% according to current guidelines. Clinical assessment included echocardiography and device interrogation. Blood samples for metabolomic analysis were collected before CRT and at 6-month follow-up. Plasma was subjected to gas chromatography-mass spectrometry and\n                      <jats:sup>1<\/jats:sup>\n                      H nuclear magnetic resonance-based metabolomic analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Totally 92 patients were enrolled, with a mean age of 67.3\u00b111.3 years (37.0% female). LVEF was significantly improved from 28.9\u00b17.6% at baseline to 36.0\u00b111.3% at 6 months (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and to 40.1\u00b112.6% at 12 months (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). After CRT, 42 metabolite features were significantly decreased compared with the baseline. The ketone bodies, including 3-hydroxybutyrate (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and acetone (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01), were reduced. A branched-chain amino acid, isoleucine, was also decreased after CRT (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01). These metabolomic changes were mainly observed in the nonischemic cardiomyopathy group, while the metabolomic profile in the ischemic cardiomyopathy group was characterized by enhanced amino acid oxidation and elevated levels of lactate and pyruvate. The improvement in LVEF positively correlated with the ratio of changes in ketone bodies and isoleucine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>CRT may modulate the systemic plasma metabolomic profile, which correlated with improvement in left ventricular function in patients with severe heart failure with reduced ejection fraction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.125.014148","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:01:24Z","timestamp":1789030884000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac Resynchronization Therapy and Circulating Metabolomic Profile in Patients With Advanced Heart Failure"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9076-7915","authenticated-orcid":true,"given":"Zhiyong","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."},{"name":"Department of Cardiology, the First Affiliated Hospital, Nanjing Medical University, China (Z.Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2464-7824","authenticated-orcid":true,"given":"Hon-Chi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7694-3617","authenticated-orcid":true,"given":"Siva K.","family":"Mulpuru","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-7238","authenticated-orcid":true,"given":"Ivan","family":"Vuckovic","sequence":"additional","affiliation":[{"name":"Metabolomics Core (I.V.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-1102","authenticated-orcid":true,"given":"Abhishek J.","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8420-4670","authenticated-orcid":true,"given":"Christopher V.","family":"DeSimone","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9835-5536","authenticated-orcid":true,"given":"Samuel J.","family":"Asirvatham","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songnan","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9786-802X","authenticated-orcid":true,"given":"Song","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (Z.Q., H.-C.L., S.K.M., A.J.D., C.V.D.S., S.J.A., S.W., C.L., S.Z., P.P.D., H.H.C., Y.-M.C.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surendra","family":"Dasari","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics (S.D., K.R.B.), Mayo Clinic, Rochester, 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