Usefulness of FDG-PET/CT for diagnosis of myocardial rejection after heart transplantation

Introduction: Acute rejection is a common problem after heart transplantation. Histopathologic diagnosis via endomyocardial biopsies is the current standard in surveillance for rejection, however, there are several limitations to diagnosis. In our institution, F-18-2-Fluoro-2-deoxy-D- glucose positron emission tomography / computed tomography (FDG-PET/CT) has been performed in post-heart transplant patients under long-term glucose restriction. Acute rejection is more likely to show abnormal myocardial accumulation, but it is expected to be difficult to distinguish from physiological accumulation. The objective of this study is to evaluate whether FDG-PET/CT can diagnose the presence of myocardial rejection after heart transplantation patients.

Methods: In our institution, 110 examinations were performed on 38 post-heart transplant patients between April 2015 and December 2021 with two FDG-PET/CT system (Discovery STE; GE healthcare, Il, USA and Biograph Vision; Siemens Healthineers, Germany). FDG injection dose (MBq) was 4 times the body weight (kg). Glucose intake was restricted for 18 hours prior to FDG administration. Inclusion criteria were 1) more than 1 year after transplantation at the time of FDG-PET/CT and 2) blood glucose level is lower than 150 mg/dl. Finally, 100 exams on 35 patients (male/female=27/6, average age at exam=49.5±12.2) were included. The accumulation pattern of the left ventricular myocardium was classified into three categories; category 1: no remarkable accumulation, category 2: heterogeneous accumulation and category 3: diffuse hyperaccumulation. Classification was determined by consensus of four nuclear medicine specialists. Maximum Standard Uptake Value (SUVmax) of left ventricle myocardium, right ventricle myocardium and blood pool were also evaluated. SUVmax ratio of the myocardium and blood pool was calculated as LV-SUVr and RV-SUVr. The presence of rejection at the time of FDG-PET/CT exam was based on a comprehensive diagnosis including myocardial biopsy and clinical symptoms by a cardiologist. The patients were divided into two groups: those who had a history of rejection after the transplantation at the time of examination (rejection group) and those who did not (normal group). The accumulation pattern, LV-SUVr, and RV-SUVr were compared between the two groups. Chi-squared test and Mann-Whitney U test were used for comparison. Differences with p less than 0.05 were considered to be statistically significant.

Results: The number of exams in normal group and in rejection group were 87 and 13. In normal group, 58 (66.7%) patients were classified as category 1, 27 (31.0%) as category 2 and 2 (2.3%) as category 3. Also in rejection group, 1 (7.7%), 6 (46.2%) and 6 (46.2%) were in category 1, 2 and 3, respectively. The frequency of category 1 was higher in normal group and category 3 was higher in rejection group with statistically significance (p<0.01). Average LV-SUVr of the normal group was significantly lower than that of the rejection group (1.55±1.16 vs 5.76±4.44; p<0.01) and also average RV-SUVr of the normal group was significantly lower than that of the rejection group (0.93±0.15 vs 1.70±1.09; p<0.01). In the rejection group, 3 patients were diagnosed as having acute rejection at the time of examination. Accumulation pattern of these 3 exams were all category 3 and RV-SUVr were higher than 2, while RV-SUVr of other exams were all lower than 2.

Conclusions: In FDG-PET/CT under long-term glucose restriction of post-heart transplant patients, the absence of diffuse FDG accumulation in left ventricle myocardium is unlikely to indicate rejection. Although the number of cases is small, diffuse high accumulation of FDG in the right ventricle has been seen only in active rejection. So, this finding is highly suggestive of rejection rather than physiological accumulation.