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Plasma cardiotrophin-1 following acute myocardial infarction: relationship with left ventricular systolic dysfunction
Suneel Talwar1, Iain B Squire, Russell J O'brien
1Department of Medicine & Therapeutics, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, U.K.
Insights
Plasma Cardiotrophin-1 (CT-1) levels are elevated after acute myocardial infarction (AMI) in humans. Early CT-1 measurements indicate left ventricular (LV) dysfunction, suggesting a role in heart failure development.
Area of Science:
- Cardiovascular Medicine
- Molecular Cardiology
- Biochemistry
Background:
- The glycoprotein 130 (gp 130) signaling pathway is crucial in heart failure pathogenesis.
- Cardiotrophin-1 (CT-1), a gp 130 pathway cytokine, influences ventricular remodeling post-acute myocardial infarction (AMI) in animal models.
Purpose of the Study:
- To investigate plasma CT-1 levels in human patients following AMI.
- To determine the relationship between CT-1 levels and left ventricular (LV) systolic function assessed by echocardiography.
Main Methods:
- Serial plasma CT-1 measurements in 60 AMI patients at multiple time points post-infarction.
- Echocardiographic assessment of LV function using a LV wall motion index (WMI) on admission (WMI-1) and at a follow-up visit (WMI-2).
Main Results:
- Plasma CT-1 concentrations were significantly elevated in AMI patients compared to controls across all measured time points.
- Higher CT-1 levels were observed following anterior compared to inferior AMI, with sustained increases in anterior AMI cases.
- WMI-1 correlated with CT-1 levels throughout hospitalization, with CT-1 at 49-72 hours post-AMI being the strongest correlate (R²=20%).
Conclusions:
- Plasma CT-1 is elevated early after human AMI and increases further in the weeks following anterior infarctions.
- Early post-AMI CT-1 levels are indicative of LV dysfunction.
- CT-1 may play a role in ventricular remodeling and the progression to heart failure after AMI.
Abstract:
The glycoprotein 130 (gp 130) signalling pathway is important in the development of heart failure. Cardiotrophin-1 (CT-1), a cytokine acting via the gp 130 pathway, is involved in the process of ventricular remodelling following acute myocardial infarction (AMI) in animals. The aims of the present study were to examine the profile of plasma CT-1 following AMI in humans, and its relationship with echocardiographic parameters of left ventricular (LV) systolic function. Serial measurements of plasma CT-1 levels were made in 60 patients at 14-48 h, 49-72 h, 73-120 h and 121-192 h following AMI and at a later clinic visit. LV function was assessed using a LV wall motion index (WMI) score on admission (WMI-1) and at the clinic visit (WMI-2). Compared with values in control subjects (29.5+/-3.6 fmol/ml), the plasma CT-1 concentration was elevated in AMI patients at 14-48 h (108.1+/-15.1 fmol/ml), 49-72 h (105.2+/-19.7 fmol/ml), 73-120 h (91.2+/-14.9 fmol/ml) and 121-192 h (118.8+/-22.6 fmol/ml), and at the clinic visit (174.9+/-30.9 fmol/ml) (P<0.0001). Levels were higher following anterior compared with inferior AMI. For patients with anterior AMI, CT-1 levels were higher at the clinic visit than at earlier times. WMI-1 correlated with CT-1 at all times prior to hospital discharge (P<0.05). On best subsets analysis, the strongest correlate with WMI-1 was CT-1 level at 49-72 h (R(2)=20%, P<0.05). In conclusion, plasma levels of CT-1 are elevated soon after AMI in humans and rise further in the subsequent weeks in patients after anterior infarction. CT-1 measured soon after AMI is indicative of LV dysfunction, and this cytokine may have a role in the development of ventricular remodelling and heart failure after AMI.