{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T17:59:35Z","timestamp":1789322375954,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T00:00:00Z","timestamp":1407369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle dysfunction in patients with heart failure (HF) has been linked to impaired growth hormone (GH)\/insulin\u2010like growth factor (IGF)\u20101 signaling. We hypothesized that ventricular assist device (VAD) implantation reverses GH\/IGF\u20101 axis dysfunction and improves muscle metabolism in HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood and rectus abdominis muscle samples were collected during VAD implantation and explantation from patients with HF and controls. Clinical data were obtained from medical records, biomarkers measured by enzyme\u2010linked immunosorbent assay (ELISA), and gene expression analyzed by reverse transcription and real\u2010time polymerase chain reaction (RT\u2010PCR). Grip strength was assessed by dynamometry. Oxidative capacity was measured using oleate oxidation rates. Muscle fiber type and size were assessed by histology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Elevated GH (0.27\u2009\u00b1\u20090.27 versus 3.6\u2009\u00b1\u20097.7\u00a0ng\/ml in HF;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002) and lower IGF\u20101 and insulin\u2010like growth factor binding protein (IGFBP)\u20103 were found in HF (IGF\u20101, 144\u2009\u00b1\u200941 versus 74\u2009\u00b1\u200945\u00a0ng\/ml in HF,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05; and IGFBP\u20103, 3,880\u2009\u00b1\u2009934 versus 1,935\u2009\u00b1\u2009862\u00a0ng\/ml in HF,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05). The GH\/IGF\u20101 ratio, a marker of GH resistance, was elevated in HF (0.002\u2009\u00b1\u20090.002 versus 0.048\u2009\u00b1\u20090.1 pre\u2010VAD;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0039). After VAD support, skeletal muscle expression of IGF\u20101 and IGFBP\u20103 increased (10\u2010fold and 5\u2010fold, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) accompanied by enhanced oxidative gene expression (CD36, CPT1, and PGC1\u03b1) and increased oxidation rates (+1.37\u2010fold;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Further, VAD implantation increased the oxidative muscle fiber proportion (38 versus 54\u00a0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031), fiber cross\u2010sectional area (CSA) (1,005\u2009\u00b1\u2009668 versus 1,240\u2009\u00b1\u2009670\u00a0\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and Akt phosphorylation state in skeletal muscle. Finally, hand grip strength increased 26.5\u2009\u00b1\u200927.5\u00a0% at 180\u00a0days on\u2010VAD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 versus baseline).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data demonstrate that VAD implantation corrects GH\/IGF\u20101 signaling, improves muscle structure and function, and enhances oxidative muscle metabolism in patients with advanced HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13539-014-0155-9","type":"journal-article","created":{"date-parts":[[2014,8,6]],"date-time":"2014-08-06T09:50:29Z","timestamp":1407318629000},"page":"297-305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Ventricular assist device implantation improves skeletal muscle function, oxidative capacity, and growth hormone\/insulin\u2010like growth factor\u20101 axis signaling in patients with advanced heart failure"],"prefix":"10.1002","volume":"5","author":[{"given":"Tuba","family":"Khawaja","sequence":"first","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aalap","family":"Chokshi","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"Ji","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko S.","family":"Kato","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Zizola","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Forman","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"},{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeyoshi","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Cardiothoracic Surgery Columbia University Medical Center  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kennel","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroo","family":"Takayama","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"},{"name":"Department of Surgery, Division of Cardiothoracic Surgery Columbia University Medical Center  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifumi","family":"Naka","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"},{"name":"Department of Surgery, Division of Cardiothoracic Surgery Columbia University Medical Center  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"George","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"},{"name":"Department of Surgery, Division of Cardiothoracic Surgery Columbia University Medical Center  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Mancini","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Schulze","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology Columbia University Medical Center  622 West 168th Street, PH 10, Room 203 10032 New York 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