with LV dysfunction may provide some insight into the pathophysiologic changes that occur at the earliest stages of LV dysfunction. To test the hypothesis that an inflammatory response is an early manifestation of LV dysfunction which precedes the development of symp- tomatic CHF, we measured IL-6 levels in 58 patients with a broad range of baseline LV ejection fractions (LVEF) and with or without clinical CHF. Methods Study population and definitions We studied 58 patients undergoing cardiac catheterization for a variety of clinical indications. There were no specific inclusion criteria other than a willingness to provide informed consent. The study protocol was approved by the institutional review board of the medical school. The clinical indications for catheterization included chronic stable angina (n = 24), atypical chest pain but an abnormal stress test (n = 20), CHF (n = 12), and evaluation of syncope (n = 2). An LVEF ≥0.55 was considered normal. On the basis of the LVEF and the clinical history, the patients were stratified into 3 groups. Group 1 (controls) had no CHF and an LVEF ≥0.55. Group 2 (asympto- matic LV systolic dysfunction) had no CHF and an LVEF <0.55. Group 3 (CHF) had clinical or radiographic evidence of CHF. Exclusions included a history of cardiac transplantation, prior coronary artery bypass surgery, ongoing treatment with corti- costeroids, or a recent (<3 months) acute coronary syndrome. Acute coronary syndromes, namely, unstable angina and non- Symptomatic congestive heart failure (CHF) is associ- ated with high circulating levels of inflammatory cyto- kines including interleukin-6 (IL-6). 1-6 Peripheral IL-6 levels correlate well with the clinical severity of CHF and have been shown to have prognostic significance. 6 We recently also reported elevated circulating IL-6 lev- els in patients with symptomatic CHF and suggested that they are not the result of cardiac release. 7 Although other cytokines such as tumor necrosis factor-α (TNF-α) are elevated in CHF and appear to have prognostic implications, 1 IL-6 may be elevated in patients with nor- mal levels of TNF-α. 5 The role of IL-6 in patients with asymptomatic left ventricular (LV) systolic dysfunction has not been well characterized. The identification of elevated immune mediators in asymptomatic patients From the a Cardiac Catheterization Laboratory, University of North Carolina Hospi- tals, Chapel Hill, NC, and the b Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Mass. Supported in part by a young investigator grant from Merck & Co., Inc (White- house Station, NJ) to E. N. D. Submitted April 18, 2000; accepted November 21, 2000. Reprint requests: Efthymios N. Deliargyris, MD, Cardiac Catheterization Labora- tory, Administrative Offices, Room 2227, UNC Hospitals, 101 Manning Dr, Chapel Hill, NC 27514. E-mail: edeliargyr@aol.com Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/113078 doi:10.1067/mhj.2001.113078 Elevated interleukin-6 levels in patients with asymptomatic left ventricular systolic dysfunction Ronald J. Raymond, MD, a Gregory J. Dehmer, MD, a Theoharis C. Theoharides, PhD, MD, b and Efthymios N. Deliargyris, MD a Chapel Hill, NC, and Boston, Mass Background Elevated interleukin-6 (IL-6) levels are present in patients with New York Heart Association (NYHA) class III and IV congestive heart failure (CHF) and are associated with a poor prognosis. We sought to determine whether ele- vated IL-6 levels are also present in patients with left ventricular (LV) dysfunction but without clinical symptoms. Methods Blood samples were obtained from the femoral artery of 58 patients who underwent cardiac catheterization for recognized clinical indications. In a subgroup of 44 patients, samples were also obtained from the femoral vein, the left main coronary artery, and the coronary sinus. Patients with prior coronary artery bypass surgery, recent acute coronary syn- drome, or steroid therapy were excluded. All samples were obtained before heparin or contrast administration. IL-6 was measured by enzyme-linked immunosorbent assay and values are expressed in picograms per milliliter. Results Three groups of patients were identified: controls, no CHF, LV ejection fraction ≥0.55 (n = 32); asymptomatic LV systolic dysfunction, no CHF, LV ejection fraction <0.55 (n = 14); and CHF, pulmonary edema (n = 12). IL-6 levels were higher at all sampling sites in both the asymptomatic LV systolic dysfunction and CHF groups compared with controls with the IL-6 levels inversely related to LV ejection fraction. Conclusions Elevated IL-6 levels are present in patients with LV dysfunction even in the absence of the clinical syn- drome of CHF. These data suggest that IL-6 may be involved in the progression of subclinical LV dysfunction to clinical CHF. IL-6 may be a marker of patients at risk for progression to clinical CHF or a novel target for therapeutic intervention. (Am Heart J 2001;141:435-8.)