Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation

Abstract

Background: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)–based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. Methods: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. Results: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P =0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P =0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P =0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. Conclusions: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. Registration: HREC/13/SVH/66 and HREC/17/SVH/80. Australian New Zealand Clinical Trials Registry: ACTRN12618000672257.

Research Highlights

“…Whether CMR could replace the invasive EMB for surveillance during the first year after cardiac transplantation has not been determined. In the present trial, 2 the authors compared CMR-based surveillance with protocol EMB surveillance for acute rejection during the first year of cardiac transplantation. The trial first had a validation phase in which simultaneous CMR and EMB were performed in 33 orthotopic cardiac transplant recipients demonstrating that by combining T1 and T2 mapping and optimizing their cutoff values, CMR was able to achieve a sensitivity of 93%, specificity of 92%, and negative predictive value of 99%.…”

Replacing the Endomyocardial Biopsy: Easier Said Than Done

“…Alternative approaches including cardiac magnetic resonance imaging have also been gaining increasing interest, although access will likely be restricted to specialized centers and cost remains a concern, as well as availability with higher patient demand. 6 There is clearly a need to consider alternative approaches that have lower cost and that may be available in local laboratories or with rapid results by commercial high-volume operations. In this issue of Transplantation, Pérez-Carrillo et al 7 from the Health Research Institute Hospital at La Fe, in Valencia, Spain, report pilot data that give us a glimpse into potential future approaches.…”

“…Alternative approaches including cardiac magnetic resonance imaging have also been gaining increasing interest, although access will likely be restricted to specialized centers and cost remains a concern, as well as availability with higher patient demand. 6…”

68 Ga-Dotatate Hybrid Positron Emission Tomography/Magnetic Resonance Imaging for Noninvasive Early Detection of Heart Transplant Rejection

“…This technique could help increase the diagnostic yield of EMB by identifying areas of inflammation and guiding PET/MR appears superior to stand-alone cardiac magnetic resonance, although rigorous evaluation was limited in this case series. Increased T2 values, a marker of inflammation/edema, have been described in ACR, 1 but with only moderate positive predictive value and limited utility in the early posttransplant stages. In contrast, 68 Ga-Dotatate-PET/MR, with its ability to detect inflammatory cells directly, accurately identified allograft rejection across a range of durations after transplant (0-13 years).…”

“…Cardiac magnetic resonance and 18F-fluorodeoxyglucose-positron emission tomography (PET) have been introduced as a complementary approach to EMB in the detection of cardiac allograft rejection; 18 F-fluorodeoxyglucose specificity, however, is limited by the uptake of normal myocardium and requires specific patient preparation, with failure of adequate myocardial suppression potentially leading to ambiguous results. 1 68 Ga-Dotatate, a somatostatin receptor type 2-binding radiotracer, has emerged as an alternative to 18 F-fluorodeoxyglucose for the evaluation of cardiovascular inflammation due to its specific binding to inflammatory cells. 2 In addition, somatostatin receptor imaging has shown promising results in the early identification of acute allograft rejection in a rat model using PET 3 and for rejection prediction in human using single-photon emission computed tomography.…”