Elevated circulating cardiotrophin-1 in heart failure: relationship with parameters of left ventricular systolic dysfunction

Cardiotrophin-1 (CT-1) is a cytokine that has been implicated as a factor i nvolved in myocardial remodelling. The objective of the present study was t o establish the relationship between circulating levels of CT-1 and measure s of left ventricular size and systolic function in patients with heart fai lure. We recruited 15 normal subjects [six male; median age 60 years (range 30-79 years)land 15 patients [11 male; median age 66 years (range 43-84 ye ars)] with a clinical diagnosis of heart failure and echocardiographic left ventricular systolic dysfunction (LVSD). Echocardiographic variables (left ventricular wall motion index, end-diastolic and -systolic volumes, stroke volume, fractional shortening) and plasma CT-1 levels were determined. In patients with LVSD [median wall motion index 0.6 (range 0.3-1.4)], CT-1 was elevated [median 110.4 fmol/ml (range 33-516 fmol/ml)] compared with contr ols [wall motion index 2 in all cases; median CT-1 level 34.2 fmol/ml (rang e 6.9-54.1 fmol/ml); P < 0.0001]. Log CT-1 was correlated with log wall mot ion index (r = -0.76, P < 0.0001), log left ventricular end-systolic volume (r = 0.54, P < 0.05), stroke volume (r = -0.60, P = 0.007) and log fractio nal shortening (r = -0.70, P = 0.001). In a multivariate model of the predi ctors of log wall motion index, the only significant predictor was log CT-1 (R-2 = 56%, P = 0.006). This is the first assessment of the relationship b etween plasma CT-1 levels and the degree of LVSD in humans, and demonstrate s that CT-1 is elevated in heart failure in relation to the severity of LVS D.