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Aguiar. Rare Dis Orphan Drugs J 2024;3:13 https://dx.doi.org/10.20517/rdodj.2023.56 Page 9 of 29

Table 3. Fabry disease cardiomyopathy biomarkers used in clinical practice
Biomarker Preclinical evaluation Clinical correlations ERT monitoring References
Cardiac troponin Not useful • LV wall thickness Remained stable during DST [79,80,86-88]
• LGE volume in cardiac
MRI
• T2 in basal inferolateral
wall
NT-proBNP Not evaluated • Diastolic dysfunction Remained stable during DST [83,86-88,91-93]
parameters and LV mass
• T2 in basal inferolateral
wall
• Inverse correlation with
T1
Echocardiogram Superior to conventional LV wall thickness ERT successfully prevented the [99-101]
(TDI) echocardiography in the detection of appearance of abnormal TDI
early cardiac involvement velocities
Echocardiogram Better sensitivity than TDI in detecting • LGE in cardiac MRI ERT improves: [93,105,106,108,109,
(speckle-tracking) early diastolic dysfunction • Functional status • Systolic strain and strain rate 118-120,122,123]
• Risk of cardiovascular (?)
events • LA peak positive strain
• Risk of WML
Cardiac MRI (LGE) LGE amount correlates Not useful: [82,93,121,124,143]
with: • LGE amount increase during
• LV mass ERT
• Regional myocardial • Major predictor of response
function to ERT
• Risk of ventricular
arrhythmias
Cardiac MRI (T1 Characteristic decrease in native T1 Staging of FD Improvement during DST, [83,85,87,88,146,
mapping) cardiomyopathy in mainly in earlier stages 150]
4 phases
ERT: Enzyme replacement therapy; HCM: hypertrophic cardiomyopathy due to sarcomere protein gene mutations; LV: left ventricle; LGE: late
gadolinium enhancement; MRI: magnetic resonance imaging; DST: disease-specific treatment; NT-proBNP: N-terminal fragment of the
prohormone of brain natriuretic peptide; TDI: tissue Doppler imaging; WML: white matter lesions; LA: left atrial; FD: Fabry disease.

in conventional parameters of diastolic dysfunction, but there was a significant decrease in myocardial
systolic and diastolic velocities, even in FD patients without LV hypertrophy (although of lesser magnitude
than in patients with overt LV hypertrophy) . These results were further confirmed in several cohorts of
[100]
patients [87,88,97-99,101,103] . Abnormalities of systolic velocities in the right ventricle (RV), measured by TDI, have
been recently described .
[104]

Furthermore, it was identified a significant inverse correlation between systolic mitral annular velocity (S′)
or early diastolic mitral annular velocity (E′) and interventricular septum (IVS) or left ventricle posterior
[101]
wall (LVPW) thickness . The diagnostic accuracy of TDI variables in detecting myocardial fibrosis was
also evaluated, with both septal and lateral E/E′ ratios, an estimate of left ventricular end-diastolic pressure,
[93]
presenting high diagnostic accuracy in predicting the presence of LGE in cardiac MRI .

Regarding treatment effect, agalsidase α successfully prevented the appearance of abnormal TDI velocities in
[102]
the group of patients with normal echocardiograms at baseline) . It was concluded that reduction in
myocardial contraction and relaxation velocities in TDI are detectable before the development of LV
hypertrophy or even abnormalities in the traditional parameters of diastolic function, thus enabling the
recognition of preclinical cardiac damage.