Myocardial inflammation in Fabry disease: correlations between myocardial histology, T2 mapping, and troponin

Abstract

Abstract Background Myocardial inflammation likely plays a key role in cardiac Fabry disease (FD), supported by the frequent observation using cardiac MRI (CMR) of high T2 mapping values, mainly in areas of late gadolinium enhancement, LGE), typically representing oedema, and increased troponin (myocardial injury). Purpose To characterize inflammation in FD cardiomyopathy by comparing myocardial histology, T2 mapping and troponin. Methods Fifteen FD patients (67% females; 51 years old, range 39-62), undergoing 3 tests: biopsy (either RV endomyocardial biopsy, n=10, or myectomy, n=5); CMR (1.5T: cines, LGE, native T1/T2 mapping quantified in the sampling area); and troponin assessment (high sensitivity TnI). Mapping values were compared to local healthy volunteers. Left ventricle hypertrophy (LVH) was defined as either MWT ≥12mm or indexed LV mass above sex specific reference ranges. Tissue was stained using Haematoxylin-Eosin and Azan Mallory trichrome. Inflammatory cell staining used CD68 and CD3 antibodies. An abnormal inflammatory infiltrate was defined according to ESC criteria as ≥14 leukocytes/mm2 (up to 4monocytes/mm2, CD3+T-lymphocytes>7cells/mm2) and its distribution classified as focal (<30% of the specimen), multifocal (30-60%), diffuse (>60%). Results Median LV ejection fraction was 63% (58-67); indexed end diastolic volume 83ml/m2 (68-91). Seven patients had LVH. 8 patients had low native T1 and 6 had infero-lateral LGE. Median septal T2 value was 50ms (47-52) with 3 (all females) above local upper limit value (ULV). TnI was increased in 6 pts (40%; median value 54ng/L [38-128]). Histology showed mild inflammatory infiltrates in 8 pts (46%), none diffuse (focal 4, multifocal 4). Seven were mixed - T lymphocytes and macrophages, one was exclusively macrophages. Inflammatory foci were quiescent (n=5), or associated to myocytes injury not typical of ischemic damage and fibrosis (n=3). None had histologically visible myocardial oedema. Patients with inflammatory infiltrates had higher T2 values (52ms [50-54] vs 47ms [46-51]; p=0.043) but the same troponin (18ng/L [3-82] vs 14ms [3-24], p=0.215) (figure 1). The 3 patients with high T2 all had inflammatory cells associated to histologic myocyte injury (figure 2). Conclusion For the first time we correlate histology with T2 and myocardial injury in FD. In this small study, mild myocardial macrophage/lymphocyte infiltrates are common in FD and are associated to higher T2 values. Abnormal T2 septal elevation is less common (it is known common in the basal inferolateral wall however) and when present, infiltration with histological myocyte damage is found.