Loss of base-to-apex circumferential strain gradient assessed by cardiovascular magnetic resonance in Fabry disease: relationship to T1 mapping, late gadolinium enhancement and hypertrophy

Abstract

Background Cardiac involvement is common and is the leading cause of mortality in Fabry disease (FD). We explored the association between cardiovascular magnetic resonance (CMR) myocardial strain, T1 mapping, late gadolinium enhancement (LGE) and left ventricular hypertrophy (LVH) in patients with FD. Methods In this prospective study, 38 FD patients (45.0 ± 14.5 years, 37% male) and 8 healthy controls (40.1 ± 13.7 years, 63% male) underwent 3 T CMR including cine balanced steady-state free precession (bSSFP), LGE and modified Look-Locker Inversion recovery (MOLLI) T1 mapping. Global longitudinal (GLS) and circumferential (GCS) strain and base-to-apex longitudinal strain (LS) and circumferential strain (CS) gradients were derived from cine bSSFP images using feature tracking analysis. Results Among FD patients, 8 had LVH (FD LVH+, 21%) and 17 had LGE (FD LGE+, 45%). Nineteen FD patients (50%) had neither LVH nor LGE (FD LVH- LGE-). None of the healthy controls had LVH or LGE. FD patients and healthy controls did not differ significantly with respect to GLS (− 15.3 ± 3.5% vs. − 16.3 ± 1.5%, p = 0.45), GCS (− 19.4 ± 3.0% vs. -19.5 ± 2.9%, p = 0.84) or base-to-apex LS gradient (7.5 ± 3.8% vs. 9.3 ± 3.5%, p = 0.24). FD patients had significantly lower base-to-apex CS gradient (2.1 ± 3.7% vs. 6.5 ± 2.2%, p = 0.002) and native T1 (1170.2 ± 37.5 ms vs. 1239.0 ± 18.0 ms, p < 0.001). Base-to-apex CS gradient differentiated FD LVH- LGE- patients from healthy controls (OR 0.42, 95% CI: 0.20 to 0.86, p = 0.019), even after controlling for native T1 (OR 0.24, 95% CI: 0.06 to 0.99, p = 0.049). In a nested logistic regression model with native T1, model fit was significantly improved by the addition of base-to-apex CS gradient (χ 2 (df = 1) = 11.04, p < 0.001). Intra- and inter-observer agreement were moderate to good for myocardial strain parameters: GLS (ICC 0.849 and 0.774, respectively), GCS (ICC 0.831 and 0.833, respectively), and base-to-apex CS gradient (ICC 0.737 and 0.613, respectively). Conclusions CMR reproducibly identifies myocardial strain abnormalities in FD. Loss of base-to-apex CS gradient may be an early marker of cardiac involvement in FD, with independent and incremental value beyond native T1.

Cardiac Imaging in Anderson-Fabry Disease: Past, Present and Future

“…Few studies have analyzed CMR-derived GLS and GCS in AFD patients. No significant differences in GLS between AFD patients and controls have been found [ 85 ]. Regarding GCS, a significant increase in circumferential strain in patients with LVH phenotype has been found, and it may imply the presence of functional cardiovascular impairment [ 86 ].…”

“…Regarding GCS, a significant increase in circumferential strain in patients with LVH phenotype has been found, and it may imply the presence of functional cardiovascular impairment [ 86 ]. Mathur et al demonstrated that base-to-apex CS gradient discriminates between AFD patients without hypertrophy or LGE and healthy controls independent of native T1, suggesting that loss of base-to-apex CS gradient may be an early marker of cardiac involvement in AFD [ 85 ]. More recently, Augusto et al described a slightly reduced GLS as a primary cardiac phenomenon, because of the altered myocardial coupling to the systemic vasculature due to systemic endothelial and smooth muscle changes [ 87 ].…”

Value of Left Ventricular Feature Tracking Strain Analysis for Detection of Early Cardiac Involvement in Fabry Disease (FD)

“…Based on their results with association of impairment in GLS and reduction of native T1 times without presence of LVH, the authors of a recent study suggested that mechanical dysfunction in the course of FD occurs before evidence of glycosphingolipid deposition [25]. Another study concluded that base to apex circumferential strain may be an early marker of cardiac FD involvement with independent and incremental value beyond native T1 [26].…”

Cardiovascular magnetic resonance (CMR) in restrictive cardiomyopathies

“…In particular, AFD patients show impairment in global longitudinal strain (GLS) correlated with myocardial damage degree (presence of LGE and cardiac biomarkers) and nT1 values, even at pre-hypertrophic stage [38]. Furthermore, AFD is characterized by reduction in global circumferential strain (GCS) and in GCS gradient from the LV base to the apex [39].…”