We sought to evaluate the relationship between plasma cytokine levels (sCD14, tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) and tissue Doppler derived indices of left ventricular systolic and diastolic function in patients with newly diagnosed heart failure. We enrolled 101 consecutive patients (mean age 65+/-13 years) with newly diagnosed heart failure who were hospitalized in our institute. Echocardiographic assessment was performed in all patients during the third day of their initial hospitalization. The pulsed tissue Doppler imaging (TDI) of the systolic and diastolic function of mitral annulus was characterized by the systolic wave Smv, and the diastolic waves: Emv and Amv. Left atrial kinetic energy (LAKE), an index of left atrial function, was calculated using the equation 1/2 x LASV x 1.06 x Amv(2); where LASV is left atrial systolic volume. Furthermore the ratio E/Emv and the flow propagation velocity were also calculated; where E is the rapid mitral filling wave, detected by pulse Doppler. Soluble plasma levels of CD14, TNF-alpha, and IL-6 were measured in all patients during their third day of hospitalization. Linear regression analysis, after adjustment for sex, age, left ventricular ejection function, body mass index, arterial hypertension, smoking, physical activity, creatinine clearance, diabetes mellitus, and blood lipid levels, revealed that IL-6 levels were inversely associated with LAKE (b= - 5422.4+/-2031.5, P=0.03), Sm (b= -0.375+/-0.1, P=0.03), and flow propagation (b= -5.404+/-0.621, P=0.001). CD14 levels were inversely associated with flow propagation (b = -17.655+/-2.6, P=0.001), and positively associated with E/Emv ratio (b=2.58+/-3.6, P=0.002) and A/Amv ratio (b=0.629+/-0.6, P=0.04). TNF-alpha was inversely associated with Smv (b-1.189+/-0.3, P=0.005). This study reveals that increased plasma levels of CD14, IL-6 and TNF-alpha are associated with impaired left atrial function and more advanced left ventricular diastolic and systolic dysfunction, in patients with newly diagnosed heart failure.