RT Journal Article
SR Electronic
T1 1 Inflammatory cardiomyopathy in fabry disease
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP A1
OP A2
DO 10.1136/heartjnl-2019-BSCMR.1
VO 105
IS Suppl 3
A1 JB Augusto
A1 S Nordin
A1 R Kozor
A1 R Vijapurapu
A1 K Knott
A1 R Hughes
A1 S Rosmini
A1 U Ramaswami
A1 T Geberhiwot
A1 RP Steeds
A1 S Baig
A1 D Hughes
A1 JC Moon
YR 2019
UL http://heart.bmj.com/content/105/Suppl_3/A1.abstract
AB Background Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in α-galactosidase A. Cardiovascular magnetic resonance (CMR) has helped unveil the pathogenesis of Fabry cardiomyopathy: sphingolipid storage (low T1 mapping values), left ventricular hypertrophy (LVH) and myocardial fibrosis with late gadolinium enhancement (LGE) characteristically present in the basal inferolateral (BIFL) wall. Recent evidence has suggested that the LGE may be inflammation and oedema as part of this pathogenic process.Purpose To assess the presence of inflammation in patients with FD using T2 mapping (for oedema/inflammation) supported by blood troponin levels (showing myocyte death and by inference inflammation).Methods A multi-centre international study in gene positive FD patients using CMR and blood biomarkers. All participants underwent CMR at 1.5 T. Native T1 and T2 mapping were performed. The T1 mapping sequence was MOLLI with sampling scheme in seconds. LGE used a phase sensitive inversion recovery sequence. Global longitudinal 2D strain (GLS) values were obtained using feature tracking analysis. Blood high-sensitivity troponin T (hsTnT) was measured on the same day.Results 100 FD patients (age 43.8±1.3 years, 42% male) were included. 45% had LVH, 35% LGE. Low T1 mapping (normal <943 ms) was found in 49% and 33% had high hsTnT values (normal <15 ng/L). Mean T2 mapping values were 52.6±0.6 ms in the BIFL wall and 49.5±0.3 ms in the remote myocardium/septum (p<0.001, normal <53 ms). T2 values in the BIFL wall were significantly higher among patients with LGE (58.2±6.1 ms vs 49.2±3.1 ms, p<0.001, figure 1). In a per-segment analysis of 1600 segments, higher T2 values correlated positively with percentage of LGE per segment (r=0,262, p<0.001), T1 values (r=0,205, p<0.001), maximum wall thickness (r=0,253, p<0.001) and GLS values (r=0,212, p<0.001). HsTnT values were higher among patients with LGE (median of 31 vs 3 ng/L in patients without LGE, p<0.001). There was a strong positive correlation between T2 values in the BIFL wall and ln(hsTnT) (r=0.776, p<0.001, figure 2). The strongest predictor of increased hsTnT in multivariate analysis (age, sex, LVH, septum T1, T2 in the BIFL, GLS, LGE) was T2 in the BIFL wall (β=0.4, p=0.001).Abstract 1 Figure 1 Box-plot graph showing T2 values in remote and BIFL (LGE) areasAbstract 1 Figure 2 Scatter-plot graph illustrating a positive correlation between T2 values in the BIFL wall and blood hsTnTAbstract 1 Figure 3 Native T1, T2 and ECV mapping values measured in the septum and basal inferolateral wall. Typical BIFL wall scar is seen. Note the increased T2 mapping values matching the areas of LGEConclusions Cardiac involvement in FD goes beyond storage (low T1 values). When LGE is present, this is almost always associated with a high T2 and troponin elevation supporting FD as a chronic inflammatory cardiomyopathy. Initial reports of LGE being fibrosis are too simplistic – LGE in FD appears to have a significant chronic inflammation/oedema component.