THU0082 Impaired left ventricular relaxation and its association with inflammatory markers in collagen-induced arthritis
Authors: L. Mokotedi, F.S. Michel, C. Mogane, P.H. Dessein, A.M. Millen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) experience an increased risk of developing heart failure with a preserved ejection fraction. Although there is some evidence to support a role of chronic inflammation in the pathogenesis of impaired left ventricular (LV) function in RA,<sup>1</sup> the direct effects of inflammatory cytokines on the LV function in collagen-induced arthritis (CIA) (an experimental model most similar to RA) require further elucidation. <h3>Objectives</h3> The aim of this study was to determine LV systolic and diastolic function and their association with circulating inflammatory markers in CIA. <h3>Methods</h3> Male Sprague Dawley rats were randomly divided into two groups: a control group (n=12) and a collagen-induced arthritis group (CIA, n=21). Rats in the CIA group were immunised with 0.2 ml type-II bovine collagen emulsified in incomplete Freund's adjuvant at the base of the tail followed by a 0.1 ml booster injection 7 days later. Eight weeks post-immunisation, markers of LV systolic function and geometry including ejection fraction (EF), fractional shortening (FS), stroke volume (SV) and LV end systolic diameter (ESD) were assessed echocardiographically using two-dimensional directed M-mode imaging. Markers of LV diastolic function including the early-to-late diastolic filling velocity ratio (E/A), the lateral (Lat e') and septal (Sep e') wall myocardial tissue lengthening at the mitral annulus and the ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') were assessed using pulsed Doppler and tissue Doppler echocardiography. Serum concentrations of interleukin 6 (IL-6), interleukin 1β (IL-1β), tumour necrosis factor alpha (TNF-α) and C-reactive protein (CRP) were determined by an enzyme-linked immunosorbent assay. <h3>Results</h3> No significant differences in markers of systolic function or geometry (EF, FS, SV and ESD) were observed between the groups (p&gt;0.05). Compared to the control group, E/A (control=2.17±0.39; CIA=1.46±0.46; p=0.0001) and Sep e' (control=3.75±0.69; CIA=3.23±0.47; p=0.04) were lower in the CIA group. By contrast, E/e' (control=29.94±6.99; CIA=24.17±8.49; p=0.13) and Lat e' (control=3.99±0.43; CIA=3.79±0.78; p=0.31) did not differ amongst the two groups. IL-6 (115±70.09 versus 365.3±88.96 pg/mL; p&lt;0.0001), IL-1β (14.1±55.7 versus 238.6±49.01 pg/mL; p&lt;0.0001), TNF-α (293.5±87.16 versus 626.0±119.7 pg/mL; p&lt;0.0001) and CRP concentrations (0.23±0.34 versus 0.97±0.35 ng/mL; p&lt;0.0001) were higher in the CIA compared to control group. A lower E/A was associated with TNF-α (r=−0.63; p=0.0003), IL-6 (−0.56; p=0.0001), IL-1β (r=−0.48; p=0.001) and CRP concentrations (r=−0.60; p=0.001) in the total sample. Lower TNF-α (r=−0.39 p=0.04) and IL-1β (r=−0.47, p=0.01) levels were associated with E/e' in the total sample. <h3>Conclusions</h3> Diastolic function is impaired in male Sprague Dawley rats with CIA. Our results indicate that exposure to high grade inflammation can reduce LV relaxation without impairing systolic function in CIA. Markers of inflammation were also associated with increased filling pressures in this animal model. Systemic inflammation may directly impact myocardial diastolic function in CIA. <h3>Reference</h3> [1] Liang KP, Myasoedova E, Crowson CS, et al. Increased prevalence of diastolic dysfunction in rheumatoid arthritis. Ann Rheum Dis. 2010;69:1665–1670. <h3>Disclosure of Interest</h3> None declared