1346918 - No access, no problem. A case of CMR-based rejection surveillance and management in a pediatric heart transplant recipient

A 19-year-old female with heterotaxy syndrome, dextrocardia, absent right superior vena cava with persistent left superior vena cava, interrupted inferior vena cava with hemiazygous continuation, and LV non-compaction cardiomyopathy, underwent heart transplantation (HT) at 14 years old due to advanced heart failure.

Her post-HT course was complicated by recurrent episodes of severe acute rejection (AR), likely secondary to medication non-adherence, and early allograft vasculopathy. Due to multiple venous occlusions, further endomyocardial biopsies (EMB) were rendered high risk. Furthermore, echocardiographic acoustic windows were suboptimal. Therefore, serial CMR were used for monitoring AR progression, which demonstrated worsening myocardial T1/ ECV, T2, new and progressive LGE, and consistent decline in biventricular function. Corroborated by persistently subtherapeutic immunosuppression (IS) troughs and increasing serum donor derived cell-free DNA (dd-cfDNA), CMR findings indicated worsening AR.

Diagnostic Techniques and Their Most Important Findings:

First CMR performed at 43 months post-HT, at the time of biopsy-proven severe AR, revealed elevated native T1 (1,105± 21 ms), ECV (25.4 ± 2.5%) and T2 (42 ± 2.8 ms) with normal LVEF (63%) and RVEF (53%). Tacrolimus and Sirolimus levels were simultaneously low ( < 2.0 ng/ml). She was treated for severe AR, and her maintenance regimen was fortified. Four months later, after losing venous access, she had a notable decline in biventricular systolic function on echocardiography, a rise in serum N-terminal pro B-type natriuretic peptide (NT pro-BNP), significantly elevated dd-cfDNA (7.8%), and intermittently subtherapeutic IS levels (Table 1, Figure 1). Repeat CMR at 49 months post-HT demonstrated further increase in T1/ECV, T2, and a decline in LV/RV EF, with new subepicardial LGE in lateral and inferolateral LV walls (Figure 2). With AR treatment, dd-cfDNA declined to 0.29%, but 2 months later, CMR showed further increases in T1 (1,237 ± 53 ms), ECV (45.9 ± 1.9%) and T2 (61 ± 2 ms), ongoing decline in LVEF (41%) and RVEF (41%), circumferential myocardial LGE extension, and new septal hypokinesis. By this time, her dd-cfDNA levels had peaked at 8%, she was tachycardic, and her ECG showed low voltages, all concerning for recurrent severe AR. Since that time, her IS has been intensified with clinical improvement and decline in dd-cfDNA (most recently 1.8%), with plans to continue serial CMR and dd-cfDNA monitoring to assess response to therapy.
 

Learning Points from this Case:

Though CMR is not typically used as the sole modality for AR monitoring, the inability to perform EMB in our patient compelled CMR-based management. Prior studies have demonstrated an association between AR and elevated T2 and ECV. In our patient, progressive increase in T1/ECV, T2 and LGE was accompanied by increased dd-cfDNA, subtherapeutic IS levels, a decline in biventricular EF, and a clinical presentation indicating worsening AR, further supporting the use of CMR-derived tissue characterization in AR surveillance.