Cardiac Function, Inflammatory Mediators and Mortality in Critical Limb Ischemia

Abstract

Patients with critical limb ischemia (CLI) have a high frequency of concomitant coronary heart disease and congestive heart failure. The aim of the study was to evaluate cardiac function in relation to inflammatory markers and 1-year mortality rate among patients with CLI. The authors investigated 232 consecutive patients with CLI by means of electrocardiogram (ECG), and measurements of endothelin (ET)-1, tumor necrosis factor alpha (TNF)alpha, interleukin (IL)-6, neopterin, CD40 ligand, and 8-epi-prostaglandin (PG)F2alpha in plasma. Echocardiography (echo) was performed in 88 (38%) patients. One-year mortality rate was assessed after prospective follow-up. One hundred and eighty-six (80%) patients had sinus rhythm (SR), 36 (16%) had atrial fibrillation or flutter (AF), and 10 (4%) pacemaker rhythm. Ischemic ECG changes occurred in 143 (62%) patients. Patients with AF showed higher IL-6 (p = 0.0296) and neopterin (p = 0.0494) concentrations. Patients with ischemic ECG changes showed higher ET-1 (p = 0.0303), 8-epi-PGF2alpha (p = 0.0027), neopterin (p = 0.0004) concentrations and 1-year mortality rate (p = 0.0105). The difference in ET-1 remained in logistic regression (p = 0.0152). Internal diameter of the left ventricle on echo correlated with IL-6 (r = 0.345, p = 0.0017), TNFalpha (r = 0.240, p = 0.0273), and neopterin (r = 0.327, p = 0.0028). Internal diameter of the left atrium correlated with TNFalpha (r = 0.384, p = 0.0092) and neopterin (r = 0.526, p = 0.0004), and ejection fraction (EF) correlated inversely with IL-6 (r = -0.380, p = 0.0015) and neopterin (r = -0.346, p = 0.0038). Patients with EF <40% showed higher (p = 0.0462) 1-year mortality rate than patients with EF >40%. In conclusion, in critical limb ischemia, cardiac rhythm disturbances and ischemic ECG changes were related to inflammatory mediators and predicted 1-year mortality rate. The inflammatory mediators correlated with echocardiographic signs of congestive heart failure.