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Elevated circulating cardiotrophin-1 in heart failure: relationship with parameters of left ventricular systolic
S Talwar1, I B Squire, P F Downie
1Department of Medicine and Therapeutics, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK.
Insights
Elevated levels of Cardiotrophin-1 (CT-1) in heart failure patients correlate with reduced left ventricular systolic function. This study shows CT-1 as a key indicator of disease severity in heart failure.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Cardiotrophin-1 (CT-1) is a cytokine linked to myocardial remodeling.
- Understanding CT-1's role in heart failure is crucial for therapeutic development.
Purpose of the Study:
- To investigate the association between circulating CT-1 levels and left ventricular (LV) size and systolic function in heart failure patients.
- To determine if CT-1 levels can predict the severity of left ventricular systolic dysfunction (LVSD).
Main Methods:
- Echocardiographic assessment of LV size and function (wall motion index, volumes, stroke volume, fractional shortening) in 15 heart failure patients and 15 controls.
- Plasma CT-1 levels were measured using immunoassays.
- Statistical analysis, including correlation and multivariate modeling, was performed.
Main Results:
- Patients with LVSD exhibited significantly higher plasma CT-1 levels compared to healthy controls (P<0.0001).
- Plasma CT-1 levels showed significant correlations with LV wall motion index (r=-0.76), end-systolic volume (r=0.54), stroke volume (r=-0.60), and fractional shortening (r=-0.70).
- Log CT-1 was the sole significant predictor of log wall motion index in a multivariate model (R(2)=56%, P=0.006).
Conclusions:
- Circulating CT-1 levels are elevated in patients with heart failure and LVSD.
- Plasma CT-1 levels are directly related to the severity of LVSD in humans.
- CT-1 may serve as a valuable biomarker for assessing heart failure severity.
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.