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

Abstract

Cardiotrophin-1 (CT-1) is a cytokine that has been implicated as a factor involved in myocardial remodelling. The objective of the present study was to establish the relationship between circulating levels of CT-1 and measures of left ventricular size and systolic function in patients with heart failure. We recruited 15 normal subjects [six male; median age 60 years (range 30-79 years)] and 15 patients [11 male; median age 66 years (range 43-84 years)] 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 controls [wall motion index 2 in all cases; median CT-1 level 34.2 fmol/ml (range 6.9-54.1 fmol/ml); P<0.0001]. Log CT-1 was correlated with log wall motion 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 fractional shortening (r=-0.70, P=0.001). In a multivariate model of the predictors 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 between plasma CT-1 levels and the degree of LVSD in humans, and demonstrates that CT-1 is elevated in heart failure in relation to the severity of LVSD.

Cardiotrophin-1 Review

“…In a multivariate model of the predictors of log wall motion index, the only signifi cant predictor was log CT-1. This demonstrates that CT-1 is elevated in heart failure in relation to the severity of LVSD 25,37 . Plasma CT-1 has high diagnostic effi cacy for heart failure (at concentration of 68 fmol/ml, sensitivity and specifi city were 95 % and 82.5 % respectively 64 ).…”

Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

“…Likewise, the level of circulating CT-1 was found to be a predictor of death or heart failure following acute myocardial infarction [73]. Most importantly, the studies in humans revealed a significant correlation between CT-1 expression, LV end-diastolic dimensions, and the severity of left ventricular systolic dysfunction [137]. CNTF could not be detected in the plasma of patients with moderate heart failure [91]; no additional data on systemic CNTF levels are available to date.…”

Augmented Expression of Cardiotrophin-1 in Failing Human Hearts Is Accompanied by Diminished Glycoprotein 130 Receptor Protein Abundance

“…These include gp130 receptor internalization and degradation and induction of intrinsic suppressor of cytokine signaling (SOCS) proteins, such as SOCS-3. 4 We and others have shown that patients with congestive heart failure have raised plasma levels of CT-1 [5][6][7] that correspond to disease severity. 6 Enhanced CT-1 secretion seems to be an early event that occurs before onset of left ventricular systolic dysfunction and therefore may have an impact on disease progression.…”

“…4 We and others have shown that patients with congestive heart failure have raised plasma levels of CT-1 [5][6][7] that correspond to disease severity. 6 Enhanced CT-1 secretion seems to be an early event that occurs before onset of left ventricular systolic dysfunction and therefore may have an impact on disease progression. 8 The observation that CT-1 concentrations were significantly higher in the coronary sinus than in the aorta 9 indicates that the heart is a prominent source of circulating CT-1 in humans.…”