Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study

Abstract

BackgroundSerial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation.MethodsAll patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation. Multiparametric CMR was prospectively performed on the same day as biopsy on four separate occasions (6 weeks, 10 weeks, 15 weeks and 20 weeks post-transplant). CMR included assessment of global and regional ventricular function, myocardial tissue characterization (T1 mapping, T2 mapping, extracellular volume, LGE) and pixel-wise absolute myocardial blood flow quantification. CMR parameters were compared with biopsy findings. As is standard, grade 2R or higher ACAR was considered significant.Results88 CMR-matched biopsies were performed in 22 patients. Eight (9%) biopsies in 5 patients demonstrated significant ACAR. Significant ACAR was associated with a reduction in circumferential strain (−12.7 ± 2.5% vs. -13.7 ± 3.6%, p = 0.047) but there was considerable overlap between groups. Whilst trends were observed between ACAR and proposed CMR markers of oedema, particularly after adjusting for primary graft dysfunction, differences were not significant. Significant improvements were seen in markers of graft structure and contractility, oedema and microvascular function over the period studied, although few parameters normalised.ConclusionsThis study provides novel insight into the myocardial injury associated with transplantation, and its recovery, however multiparametric CMR was not able to accurately detect ACAR during the early phase post-transplantation.

The Value of Cardiovascular Magnetic Resonance in Heart Transplant Patients

“…Also, importantly, both studies included patients beyond 1 year post-transplant, thus reducing the effect of transplant-related myocardial injury, described above, on T 2 measurements, but also missing the window in which early detection of ACAR is thought to be most useful. In a recent study in which 22 patients were each scanned on four occasions over the first 6 months posttransplant (unselected on the basis of rejection), there was no significant difference in T 2 values between significant and non-significant rejection [5]. In part, this may reflect the small numbers of rejection episodes, but also, as described above, raised T 2 (and T 1 ) values were commonly observed in the early period post-transplant irrespective of rejection status, thus limiting the ability of CMR T 2 to detect rejection.…”

“…Nevertheless, ejection fraction is usually preserved in the newly transplanted heart. Abnormalities in myocardial strain and long axis function however are detectable and work performed using multiparametric CMR has demonstrated evidence of myocardial oedema during the first 5 months post-transplant, independent of rejection, with globally elevated myocardial T 1 and T 2 relaxation times [5]. Myocardial perfusion reserve, indicative of microvascular dysfunction, also appears to be impaired during this period.…”

Magnetic resonance imaging of the transplanted pediatric heart as a potential predictor of rejection

“…Acute rejection is characterized histologically by inflammation of the myocardium while chronic or repeated episodes of rejection have been associated with fibrotic remodeling[7,23,24]. Native T1 and ECV have been explored as markers of ACR in a pilot study in adults after HT but an association with rejection has yet to be demonstrated[8]. In the current study, albeit in a limited number of patients, ECV and native T1 times did not distinguish between < 2R and ≥ 2R ISHLT rejection.…”

“…However, CMR measurements used in adults for the detection of rejection or myocardial inflammation, including T2-weighted imaging[5,6], native T1 times and extracellular volume fractions (ECVs) derived from T1 mapping[7], myocardial thickness, ventricular volumes and ejection fraction (EF)[8,9] have not been systematically evaluated in pediatric HT recipients with EMB-proven ACR.…”

Review of Journal of Cardiovascular Magnetic Resonance 2015

“…The use of techniques to characterise components of myocardial injury, [113] myocardial edema, myocardium at risk, myocardial hemorrhage, [114] microvascular obstruction [115] and hibernation, [116] has also grown.…”