Abstract 18120: Variants of Toll Like Receptor 4 Have Prognostic Value in Patients with Dilated Cardiomyopathy

Abstract

Background - Dilated cardiomyopathy (DCM) may attend with innate immune activation, but its prognostic value is largely unknown. Since the innate immune Toll-like receptor 4 (TLR4) has been shown to be involved in atherosclerosis, we investigated the impact of coding polymorphisms of TLR4 on development and prognosis of DCM in patients. Methods and results - Two previously reported genetic variants of TLR4 (rs4986790, TLR4 c.1187A>G, p.299D>G and rs4986791,TLR4 c.1487C>T, p.T399I) were investigated. Coronary artery disease and other reasons for heart failure were excluded by angiography, myocardial biopsy, two dimensional echocardiography and spirometry. There were no significant differences between genetically defined subgroups with respect to baseline risk factors, age, gender and treatment. Presence of the rs4986790 and/or the rs4986791 variant, respectively, was not associated with an increased incidence of DCM. In contrast, patients carrying both the rs4986790 and the rs4986791 variant showed significantly reduced improvement of left ventricular (LV) ejection fraction (P=0.006) and LV dilation (P=0.015) at the follow-up evaluation when compared to carriers of the wildtype gene and isolated rs4986790 or rs4986791 variants, respectively (Figure 1). This was associated with significantly reduced levels of nt-pro brain natriuretic peptide (BNP) in patients carrying the TLR4 wildtype gene and isolated TLR4 variants at the follow-up when compared to the first admissions evaluation. Carriers of both variants did not show a significant decrease of nt-pro BNP. Conclusion - Among patients with DCM, the common presence of the TLR4 variants rs4986790 and rs4986791 predict worsened LV ejection fraction, LV dilation and nt-pro BNP levels at the course of time.