Cardiovascular Magnetic Resonance Imaging in the Evaluation of Cardiac Transplantation

Background

ACAR is a T-lymphocyte-mediated process, eventually affecting host immune responses to the transplanted heart and causing diffuse myocardial inflammation, myocytolysis, graft dysfunction, and even death. There are extensive pathologic similarities between acute rejection and other forms of inflammatory cardiomyopathies such as viral myocarditis, which are often indistinguishable on histopathology. The incidence of acute rejection is highest in the first year, at approximately 25%, and accounts for 8% of early posttransplant deaths. The current gold standard for the detection and grading of acute rejection is histopathologic assessment of EMB samples. The International Society of Heart and Lung Transplantation (ISHLT) published standardized criteria to grade the severity of rejection : grade 0R, no signs of rejection; grade 1R, mild; grades 2R and 3R, moderate and severe, respectively; and grades 2R and 3R, generally thought to be clinically relevant.

The clinical presentation of acute rejection ranges from asymptomatic to cardiogenic shock and necessitates frequent screening with as many as 13 EMBs in the first year alone. EMB is uncomfortable for heart transplant recipients, can damage the cardiac allograft, and diagnostic accuracy can be adversely affected by sampling error and pathologic expertise. Some reports suggest that 20% of acute rejection episodes have a false-negative EMB and are treated on clinical grounds alone.

CMR has the potential to be a sensitive test to screen for acute rejection, using many of the same sequences that have been helpful in nontransplant inflammatory myopathies.

T2 Cardiovascular Magnetic Resonance Imaging

T2-weighted CMR imaging can demonstrate myocardial edema and has proven utility in assessing a variety of inflammatory cardiomyopathies, including myocarditis, takotsubo cardiomyopathy, and cardiac sarcoidosis. Increased myocardial edema accompanying acute rejection has been recognized since the early 1980s and has been assessed both semiquantitatively, using a signal intensity ratio, and quantitatively, via T2 relaxation times.

Signal Intensity Ratio

Short-inversion time inversion recovery (STIR) techniques use a triple inversion recovery pulse sequence with long echo times (TEs) to produce images in which myocardial signal intensity is proportional to water content. These T2-weighted (T2W) images can be analyzed semiquantitatively by comparing the signal intensity of the myocardium with the signal intensity of skeletal muscle within the field of view. Myocardial edema is present when the myocardial signal intensity is more than twice that of skeletal muscle myocardium. Increased myocardial edema by T2 signal intensity ratio is a key component of the Lake Louise Criteria for myocarditis.

Aherne et al. was one of the first to demonstrate that increased T2 signal intensity in rejecting dog hearts was linearly correlated with ex vivo myocardial water content and could be prevented with the immunosuppressant cyclosporine. Studies of signal intensity ratio in human heart transplant recipients have had mixed results. Krieghoff et al. and Taylor et al. demonstrated that T2 signal intensity ratio increased from 1.7 to 2.1 during clinically significant rejection. Sensitivity and specificity of T2 signal intensity were modest, at 63% and 78%, respectively.

In general, STIR-based T2 signal intensity ratio has not demonstrated sufficient sensitivity in diagnosing ACAR to warrant its use as a stand-alone clinical diagnostic tool to detect rejection.