Orthotopic heart transplantation (OHT) is the standard treatment for patients with end-stage heart failure.1 However, acute cardiac allograft rejection (ACAR) is the leading cause of mortality and morbidity in the first year after transplantation. These patients undergo routine surveillance endomyocardial biopsy (EMB) to assess for ACAR. Researchers from St. Vincent’s Hospital in Sydney report a new methodology for using cardiac magnetic resonance (CMR) imaging similar to the EMB-based surveillance strategy.2
Researchers recruited 33 OHT recipients in 2014; these patients underwent surveillance EMB and CMR was performed within 24 hours of EMB during the first year post-transplantation to expand the validation cohort and compare it to healthy controls. Standard T1 and T2 multiparameter mapping thresholds were defined for the ACAR, which was used in the follow-up study. Subsequently, the researchers performed a randomized, prospective, non-inferiority study recruiting 20 patients in each arm comparing monitoring based on EMB or CMR 4 weeks after OHT. These patients underwent monitoring based on EMB or CMR at 4, 6, 8, 10, 12, 16, 20, 24 and 32 weeks after transplantation.2
In the validation cohort, OHT recipients underwent 108 EMB and CMR and were compared to the healthy cohort. This study yielded a receiver operating curve (ROC) analysis to identify high grade rejection by CMR with an AUC of 0.897 for T1 and 0.938 for T2 mapping for high grade rejection. There was high inter-observer agreement and correlation for overall T1, T2 and interventricular septum and left ventricular values. However, the sensitivity to detect low-grade rejection by CMR was modest (AUC of 0.697 for T1 and 0.689 for T2).2
In the prospective cohort, surveillance based on CMR was non-inferior to EMB in a one-year follow-up to identify high- and low-grade rejection. Interestingly, there was no significant difference in the infection event rate in the two arms. The CMR group had fewer unplanned hospitalizations (9 versus 18, p
Distinguished CMR researcher and Chief of Cardiology at the University of Virginia, Professor Dr. Christopher Kramer comments: “This is a very intriguing single center proof-of-principle study of the use of T1 and T2 CMR mapping to diagnose and treat myocardial transplant rejection. . They demonstrated excellent accuracy of CMR parametric mapping for diagnosing ACAR in the shunt group. In the validation group, there were significantly fewer biopsies in the CMR group and no difference in events, although the numbers were small. It is essentially a feasibility study as concluded by the authors.
Study strengths include careful study design and use of derivation and validation cohorts and biopsy-free randomization. Weaknesses include the single-center nature and the small n, especially in the validation group, leading to possible beta error. Each scan and field strength has different normal values for T1 and T2, making a multicenter study necessary, but difficult, to normalize these values between centers. Measurement of extracellular volume would normalize this in all centers, but requires infusion of gadolinium contrast material. Larger multicenter studies are needed to make this concept a reality, but the promise is there and is quite exciting for transplant recipients, potentially obviating the need for multiple biopsies.
- Singh TP, Mehra MR, Gauvreau K. Long-term survival after heart transplantation in centers stratified by short-term performance. Circulation: Heart failure. 2019;12(11):e005914.
- Anthony C, Imran M, Pouliopoulos J, et al. Cardiovascular magnetic resonance for monitoring rejection after heart transplantation. Traffic.0(0):10.1161/CIRCULATIONAHA.1121.057006.