{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:06:12Z","timestamp":1773425172696,"version":"3.50.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,1,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Myocardial fibrosis is an important contributor for development of diastolic dysfunction. We investigated the impact of sirolimus as primary immunosuppression on diastolic dysfunction and fibrosis progression among heart transplantation recipients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In 100 heart transplantation recipients who were either treated with a calcineurin inhibitor (CNI) (n=51) or converted from CNI to sirolimus (n=49), diastolic function parameters were assessed using serial echocardiograms and right heart catheterizations. Myocardial fibrosis was quantified on serial myocardial biopsies. After 3\u00a0years, lateral e\u2032 increased within the sirolimus group but decreased in the CNI group (0.02\u00b10.04 versus \u22120.02\u00b10.04\u00a0m\/s delta change;\n              <jats:italic>P<\/jats:italic>\n              =0.003, respectively). Both pulmonary capillary wedge pressure and diastolic pulmonary artery pressure significantly decreased in the sirolimus group but remained unchanged in the CNI group (\u22121.50\u00b12.59 versus 0.20\u00b12.20\u00a0mm\u00a0Hg\/year;\n              <jats:italic>P<\/jats:italic>\n              =0.02; and \u22121.72\u00b13.39 versus 0.82\u00b12.59\u00a0mm\u00a0Hg\/year;\n              <jats:italic>P<\/jats:italic>\n              =0.005, respectively). A trend for increased percentage of fibrosis was seen in the sirolimus group (8.48\u00b13.17 to 10.10\u00b13.0%;\n              <jats:italic>P<\/jats:italic>\n              =0.07) as compared with marginally significant progression in the CNI group (8.76\u00b13.87 to 10.56\u00b14.34%;\n              <jats:italic>P<\/jats:italic>\n              =0.04). The percent change in fibrosis did not differ significantly between the groups (1.62\u00b14.67 versus 1.80\u00b15.31%, respectively;\n              <jats:italic>P<\/jats:italic>\n              =0.88).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Early conversion to sirolimus is associated with improvement in diastolic dysfunction and filling pressures as compared with CNI therapy. Whether this could be attributed to attenuation of myocardial fibrosis progression with sirolimus treatment warrants further investigation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.018186","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T10:27:01Z","timestamp":1608114421000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Impact of Sirolimus as a Primary Immunosuppressant on Myocardial Fibrosis and Diastolic Function Following Heart Transplantation"],"prefix":"10.1161","volume":"10","author":[{"given":"Hilmi","family":"Alnsasra","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabea","family":"Asleh","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"},{"name":"Department of Cardiology Hadassah University Medical Center Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae K.","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3239-6460","authenticated-orcid":false,"given":"Joseph J.","family":"Maleszewski","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-5313","authenticated-orcid":false,"given":"Amir","family":"Lerman","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Toya","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishnaswamy","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie C.","family":"Bois","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1882-0958","authenticated-orcid":false,"given":"Sudhir S.","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33093-3"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.3.872"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005791512974"},{"key":"e_1_3_1_5_2","first-page":"II289","article-title":"Early Doppler echocardiographic dysfunction is associated with an increased mortality after orthotopic cardiac transplantation","volume":"94","author":"Ross HJ","year":"1996","unstructured":"Ross HJ, Gullestad L, Hunt SA, Tovey DA, Puryear JB, McMillan A, Stinson EB, Valantine HA. 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