168 Chapter 5 Plasma lysoGb3 and the functional parameters on echocardiography Functional parameters on echocardiography were assessed in a subset of patients. Insufficient data of male patients with classical FD, especially above the age of 30, were available to be able to include them in these analyses on the relationship between plasma lysoGb3 levels and these parameters. In the remaining patient groups (145 patients, median number of measurements per patient was 1, range 1-2), we studied the relationship between plasma lysoGb3 levels and functional echocardiography parameters related to diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) [23]. Higher plasma lysoGb3 levels were significantly related to lower e’ (mitral annular early diastolic velocity, p<0.001, fig 5a) as well as higher E/e’ (the ratio between early mitral inflow velocity and mitral annular early diastolic velocity, p=0.008, fig 5b) at any age. No significant association of lysoGb3 on progression over time (slope) for these markers was found. Higher plasma lysoGb3 levels were significantly related to a faster increase in left atrial volume index (LAVI, p=0.001) over time. Figure 5: Association between plasma lysoGb3 levels and functional parameters on echocardiography in untreated FD patients. (a) Association of plasma lysoGb3 with e’ (p<0.001). e’ represents the velocity of mitral annular motion during early diastole, and is a marker for myocardial relaxation. Patients with higher lysoGb3 values had lower e’ (suggesting stiffer LV) at any age, there was no difference in slope (b) Association of plasma lysoGb3 with E/e’ (p<0.001). E/e’ indicates the ratio between mitral inflow velocity during early diastole (E) and e’, and represents a marker for left atrial filling pressure. Patients with higher lysoGb3 values had higher E/e’ (suggesting higher filling pressure) at any age, there was no difference in slope (c) Association of plasma lysoGb3 and left atrial volume index (LAVI). Higher lysoGb3 levels were associated with a faster increase over time (p=0.003). The dotted lines in every figure represent the cutoff values for diastolic dysfunction as recommended by the European Association of Cardiovascular Imaging/American Society of Echocardiography (EACVI/ASE) [24]. In a healthy heart, relaxation of the LV causes a high velocity of the mitral annulus during early diastole (high e’) resulting in blood being ‘sucked’ from the LA into the LV. Under these circumstances, E/e’ is low, usually <8. In the presence of diastolic dysfunction due to LV hypertrophy and stiffening, the LV does not relax properly (e’ becomes lower), and as a result E/e’ increases. E/e´ >14 is highly suggestive of elevated filling pressures. Chronic increase of LA pressure resulting LA dilatation, as indicated by an increased LAVI. All analyses are performed with actual plasma lysoGb3 levels (after log10 transformation). LysoGb3 levels are grouped for visualization purposes only as described in the legend.
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