1349997 - Antibody-Mediated Rejection Mimicking Cardiac Amyloidosis in a Heart Transplant Patient: A CMR Conundrum

Description of Clinical Presentation: A 63-year-old man 10 years post heart transplant for nonischemic cardiomyopathy presented with heart failure symptoms, progressive left ventricular (LV) dysfunction, and elevated donor-specific HLA antibodies (DSA). Endomyocardial biopsy (EMB) did not demonstrate cellular or antibody mediated rejection (AMR); repeat EMB 6 weeks later was also negative. The patient had no clinical improvement and ejection fraction (EF) remained reduced despite guideline-directed medical therapy. Right heart catheterization revealed severely elevated biventricular filling pressures and reduced Fick cardiac index (1.8 L/min/m2). A cardiac MRI (CMR) was performed for further evaluation and demonstrated moderately reduced LV systolic function, severely reduced RV systolic function, and diastolic septal flattening. Diffuse circumferential late gadolinium enhancement (LGE) with significant elevation of native T1, T2 and ECV values was identified, which raised the possibility for cardiac amyloidosis. Laboratory work-up for AL amyloidosis as well as a PYP scan for TTR amyloidosis were negative. Prior EMB sample was sent for Congo red staining and was negative. Repeat EMB subsequently demonstrated AMR concordant with the persistently elevated DSA. He was treated with high dose glucocorticoids, plasma exchange, intravenous immunoglobulin, and increased immunosuppressive therapy. Repeat CMR 3 months later showed interval improvement in biventricular function with persistent diffuse circumferential LGE and elevated native T1 and T2; EMB was negative for AMR although DSA remained elevated.

Diagnostic Techniques and Their Most Important Findings: CMR images, acquired on a 1.5T Siemens Sola magnet, demonstrated moderate asymmetric septal hypertrophy with a small LV cavity, moderately reduced global LV systolic function, and severely reduced RV systolic function. Parametric mapping, using ShMOLLI method at the mid-ventricle level, demonstrated significantly elevated native T1, T2, and ECV values, consistent with diffuse myocardial fibrosis, inflammation, and edema. There was poor nulling of the myocardium as well as diffuse circumferential late gadolinium enhancement throughout the LV, which raised suspicion for cardiac amyloidosis. Interestingly, the patient’s laboratory and nuclear medicine work-up for amyloidosis was unrevealing. Repeat EMB ultimately showed AMR and he received appropriate treatment. Follow up CMR showed similar LGE pattern and persistently elevated T1 and T2 though biventricular function had improved.

Learning Points from this Case: CMR provides excellent non-invasive myocardial tissue characterization. Cardiac amyloidosis and AMR may present similarly on CMR, particularly with a diffuse pattern of LGE, as well as elevated native T1, T2, and ECV. Increased utilization of CMR in the transplant patient population may lead to greater recognition of certain tissue characteristics consistent with AMR which may guide therapeutic interventions sooner.