Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study

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 (tau(ic)), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 +/- 0.06 vs. 0.28 +/- 0.03, p < 0.0001; tau(ic): 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 ae<yen>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 tau(ic)) 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.