title: Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study.
abstract: After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. orcfilho@unicamp.br.|Discipline of Cardiology, Department of Internal Medicine, Hospital das Clínicas, State University of Campinas, UNICAMP, Rua Vital Brasil, 251-Cidade Universitária "Zeferino Vaz", Campinas-SP, São Paulo, CEP 13083-888, Brazil. orcfilho@unicamp.br.|Fundação Centro Médico de Campinas, Campinas, São Paulo, Brazil. orcfilho@unicamp.br.
authors.forename: Otavio Rizzi
authors.identifier: http://orcid.org/0000-0003-4428-5186
authors.initials: OR
authors.lastname: Coelho-Filho
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Shah
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Carlos Fernando Ramos
authors.initials: CFR
authors.lastname: Lavagnoli
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Barros
authors.affiliation: Massaschussetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Tomas G
authors.initials: TG
authors.lastname: Neilan
authors.affiliation: Cardiovascular Medicine Division, Department of Medicine, University of Michigan, Ann Arbor, MI, USA.|Nuclear Medicine Division, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Venkatesh L
authors.initials: VL
authors.lastname: Murthy
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Pedro Paulo Martins
authors.initials: PPM
authors.lastname: de Oliveira
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Jose Roberto Matos
authors.initials: JRM
authors.lastname: Souza
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Elaine Soraya Barbosa
authors.initials: ESB
authors.lastname: de Oliveira Severino
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Karlos Alexandre
authors.initials: KA
authors.lastname: de Souza Vilarinho
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Lindemberg
authors.initials: L
authors.lastname: da Mota Silveira Filho
authors.affiliation: Massaschussetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Garcia
authors.affiliation: Massaschussetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Otavio Rizzi
authors.initials: OR
authors.lastname: Coelho
authors.affiliation: Noninvasive Cardiovascular Imaging Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.|Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Jerosch-Herold
authors.affiliation: Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.|Division of Cardiothoracic Surgery, Section of Pediatric Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Orlando
authors.initials: O
authors.lastname: Petrucci
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D001706:Biopsy; D006332:Cardiomegaly / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012307:Risk Factors; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
keywords: Extracellular volume fraction; Fibrosis; Gadolinium-DTPA; Hypertrophy; Magnetic resonance imaging and orthotopic heart transplantation