{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T06:28:53Z","timestamp":1774765733432,"version":"3.50.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1995,4]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            The rate of progression and potential long-term consequences of isolated foci of moderate acute rejection (FMR) on endomyocardial biopsy (EMB) have not been defined; therefore, whether FMR necessitates augmented immunosuppression remains controversial.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            At our institution, recipients with EMBs having FMR, defined as one or two isolated foci of cellular infiltrates with associated myocyte damage (International Society for Heart and Lung Transplantation [ISHLT] grade 2 and a subset of grade 3A), do not routinely receive intensified immunosuppression. Accordingly, to determine the outcome of untreated FMR, we reviewed 4398 EMBs (mean, 4.4 samples each) obtained after orthotopic heart transplantation in 208 consecutive recipients maintained on triple immunosuppressive therapy. The incidence of progression versus resolution of FMR, the time interval after transplantation when FMR was detected, and the relation of untreated FMR to recipient survival were analyzed. FMR categorized as one (n=312) or two (n=89) foci was present in 401 EMBs (9% of total) obtained 10 days to 7.5 years after transplantation from 149 recipients (72%). EMBs with FMR resolved without treatment in 341 of 401 (85%), and only 60 of 401 (15%) progressed to higher grade rejection. EMBs that progressed occurred 7.5\u00b17.9 months (mean\u00b1SD) after transplantation compared with 14.0\u00b116.5 months after transplantation for those that resolved (\n            <jats:italic>P<\/jats:italic>\n            &lt;.005). Of the 60 EMBs that progressed, 55% occurred within the first 6 months, 78% within the first year, and 97% within the first 2 years after transplantation. EMBs with two foci of FMR were no more likely to progress than those with one focus. Thirty-nine recipients experienced one (n=25), two (n=9), three (n=3), or four (n=2) episodes of FMR that progressed. One or more episodes of FMR that did not progress occurred in 110 recipients. By Kaplan-Meier analysis, survival at 1 and 5 years was similar in recipients with and those without FMR progression.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            First, untreated FMR consisting of either one or two foci has a low rate of progression. Second, progression of FMR decreases with increasing postoperative interval and becomes rare after 2 years. Last, FMR progression did not identify recipients with decreased survival.\n          <\/jats:p>","DOI":"10.1161\/01.cir.91.7.1975","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:34:42Z","timestamp":1339461282000},"page":"1975-1980","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Natural History of Focal Moderate Cardiac Allograft Rejection"],"prefix":"10.1161","volume":"91","author":[{"given":"Gayle L.","family":"Winters","sequence":"first","affiliation":[{"name":"From the Department of Pathology (G.L.W., F.J.S.) and Cardiovascular Division, Department of Medicine (E.L.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Loh","sequence":"additional","affiliation":[{"name":"From the Department of Pathology (G.L.W., F.J.S.) and Cardiovascular Division, Department of Medicine (E.L.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick J.","family":"Schoen","sequence":"additional","affiliation":[{"name":"From the Department of Pathology (G.L.W., F.J.S.) and Cardiovascular Division, Department of Medicine (E.L.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"587","volume":"9","year":"1990","unstructured":"Billingham ME, Cary NRB, Hammond EH, Kemnitz J, Marboe C, McAllister HA, Snover DC, Winters GL, Zerbe A. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: heart rejection study group. J Heart Transplant. 1990;9:587-593.","journal-title":"J Heart Transplant"},{"key":"e_1_3_2_2_2","first-page":"319","volume":"1","year":"1988","unstructured":"Billingham ME. The postsurgical heart: the pathology of cardiac transplantation. Am J Cardiovasc Pathol. 1988;1:319-334.","journal-title":"Am J Cardiovasc Pathol"},{"key":"e_1_3_2_3_2","first-page":"22A","volume":"4","year":"1991","unstructured":"Winters GL, Johnson MR, Costanzo-Nordin MR. Prognostic significance of mild acute rejection. Mod Pathol. 1991;4:22A. Abstract.","journal-title":"Mod Pathol"},{"key":"e_1_3_2_4_2","unstructured":"Yeoh TK Frist WH Eastburn TE Atkinson J. Clinical significance of mild rejection of the cardiac allograft. Circulation. 1992;86(suppl II):II-267-II-271."},{"key":"e_1_3_2_5_2","first-page":"751","volume":"11","year":"1992","unstructured":"Lloveras JJ, Escourrou G, Delisle MB, Fournial G, Cerene A, Bassanetti I, Durand D. Evolution of untreated mild rejection in heart transplant recipients. J Heart Lung Transplant. 1992;11:751-756.","journal-title":"J Heart Lung Transplant"},{"key":"e_1_3_2_6_2","first-page":"269","volume":"9","year":"1990","unstructured":"O\u2019Connell JB, Renlund DG. Variations in the diagnosis, treatment, and prevention of cardiac allograft rejection: the need for standardization? J Heart Transplant. 1990;9:269-271.","journal-title":"J Heart Transplant"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90814-H"},{"key":"e_1_3_2_8_2","first-page":"23A","volume":"6","year":"1993","unstructured":"Fyfe B, Loh E, Couper GS, Schoen FJ: Early ischemic injury in post-transplant endomyocardial biopsies: morphology and clinical significance. Mod Pathol. 1993;6:23A. Abstract.","journal-title":"Mod Pathol"},{"key":"e_1_3_2_9_2","first-page":"26A","volume":"7","year":"1994","unstructured":"Bell G, Lones M, Czer LSC, Miller JM, Harasty D, Trento A, Fishbein MC. Grade 2 cellular cardiac rejection: does it exist? Mod Pathol. 1994;7:26A. Abstract.","journal-title":"Mod Pathol"},{"key":"e_1_3_2_10_2","first-page":"355","volume":"12","year":"1993","unstructured":"Kobashigawa J, Kirklin JK, Naftel DC, Bourge RC, Ventura HO, Mohanty PK, Cintron GB, Bhat G, and the Transplant Cardiologists Research Database Group. Pretransplantation risk factors for acute rejection after heart transplantation: a multiinstitutional study. J Heart Lung Transplant. 1993;12:355-366.","journal-title":"J Heart Lung Transplant"},{"key":"e_1_3_2_11_2","unstructured":"Kirklin JK Naftel DC Bourge RC White-Williams C Caulfield JB Tarkka MR Holman WR Zorn GL. Rejection after cardiac transplantation: a time-related risk factor analysis. Circulation. 1992;86(suppl II):II-236-II-241."},{"key":"e_1_3_2_12_2","first-page":"3665","volume":"21","year":"1989","unstructured":"Billingham ME. Graft coronary disease: the lesions and the patients. Transplant Proc. 1989;21:3665-3666.","journal-title":"Transplant Proc"},{"key":"e_1_3_2_13_2","first-page":"349","volume":"8","year":"1989","unstructured":"Johnson DE, Gao SZ, Schroeder JS, DeCampli WM, Billingham ME. The spectrum of coronary artery pathologic findings in human cardiac allografts. J Heart Transplant. 1989;8:349-359.","journal-title":"J Heart Transplant"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/1050-1738(91)90041-C"},{"key":"e_1_3_2_15_2","unstructured":"Olivari MT Kubo SH Braunlin EA Bolman RM Ring WS. Five-year experience with triple-drug immunosuppressive therapy in cardiac transplantation. Circulation. 1990;84(suppl IV):IV-276-IV-280."},{"key":"e_1_3_2_16_2","unstructured":"Hess ML Hastillo A Mohanakumar T Cowley MJ Vetrovac G Szentpetery S Wolfgang TC Lower RR. Accelerated atherosclerosis in cardiac transplantation: role of cytotoxic B-cell antibodies and hyperlipidemia. Circulation. 1983;68(suppl II):II-94-II-101."},{"key":"e_1_3_2_17_2","unstructured":"Petrossian GA Nichols AB Marboe CC Sciacca R Rose EA Smith CR Cannon PJ Reemtsma K Powers ER. Relation between survival and development of coronary artery disease and anti-HLA antibodies after cardiac transplantation. Circulation. 1989;80(suppl III):III-122-III-125."},{"key":"e_1_3_2_18_2","first-page":"871","volume":"137","year":"1990","unstructured":"Hruban RH, Beschorner WE, Baumgartner WA, Augustine SM, Ren H, Reitz BA, Hutchins GM. Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis. Am J Pathol. 1990;137:871-882.","journal-title":"Am J Pathol"},{"key":"e_1_3_2_19_2","first-page":"827","volume":"4","year":"1987","unstructured":"Uretsky BF, Murali S, Reddy PS, Rabin B, Lee A, Griffith BP, Hardesty RL, Trento A, Bahnson HT. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation. 1987;4:827-834.","journal-title":"Circulation"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/1010-7940(90)90206-F"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(19)35592-8"},{"key":"e_1_3_2_22_2","first-page":"339","volume":"9","year":"1990","unstructured":"Pucci AM, Forbes RD, Billingham ME. Pathologic features in long-term cardiac allografts. J Heart Transplant. 1990;9:339-345.","journal-title":"J Heart Transplant"},{"key":"e_1_3_2_23_2","first-page":"364","volume":"9","year":"1990","unstructured":"Winters GL, Kendall TJ, Radio SJ, Wilson JE, Costanzo-Nordin MR, Switzer BL, Remmenga JA, McManus BM. Post-transplant obesity and hyperlipidemia: major predictors of severity of coronary arteriopathy in failed human heart allografts. J Heart Transplant. 1990;9:364-371.","journal-title":"J Heart Transplant"},{"key":"e_1_3_2_24_2","first-page":"38","volume":"10","year":"1991","unstructured":"Stovin PGI, Sharples L, Hutter JA, Wallwork J, English TAH. Some prognostic factors in the development of transplant-related coronary artery disease in human cardiac allografts. J Heart Lung Transplant. 1991;10:38-44.","journal-title":"J Heart Lung Transplant"},{"key":"e_1_3_2_25_2","first-page":"S90","volume":"11","year":"1992","unstructured":"Costanzo-Nordin MR. Cardiac allograft vasculopathy: relationship with acute cellular rejection and histocompatibility. J Heart Lung Transplant. 1992;11:S90-S103.","journal-title":"J Heart Lung Transplant"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(90)90037-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.62.2.123"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.91.7.1975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T15:52:29Z","timestamp":1715529149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.91.7.1975"}},"subtitle":["Is Treatment Warranted?"],"short-title":[],"issued":{"date-parts":[[1995,4]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1995,4]]}},"alternative-id":["10.1161\/01.CIR.91.7.1975"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.91.7.1975","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,4]]},"assertion":[{"value":"1994-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1994-11-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}