The effect of valvular regurgitation on plasma Cardiotrophin-1 in patientswith normal left ventricular systolic function

Background: Cardiotrophin-1 (CT-1), a member of the interleukin-6 related c ytokine family that act via the gp130 signalling pathway, has been shown to stimulate the assembly of sarcomeric units in series in cardiomyocytes res ulting in eccentric hypertrophy, ventricular dilatation and finally loss of function. In situations of volume overload a similar form of eccentric hyp ertrophy occurs with time. Aims: We hypothesised that plasma CT-1 would be raised in patients with significant mitral, tricuspid and/or aortic regurgi tation (MR/TR or AR, respectively) when compared to those with no (or mild) valvular regurgitant lesion. Methods: A novel competitive immunoluminometr ic assay using an in-house polyclonal antibody to amino acids 105-120 of th e CT-1 sequence was developed. Seventy-eight patients (31 male, mean +/- S. D. age 63.5 +/- 17.9 years), all with normal left ventricular systolic func tion were studied. Results are expressed as mean +/- S.D. fmol/ml. Results: Sixty-three subjects had no significant valvular lesion, seven had moderat e/severe MR, nine had moderate/severe TR and four had moderate/severe AR. T hese subjects had CT-1 concentrations of 53.3 +/- 23.2, 90.5 +/- 44.4, 72.6 +/- 43.8 and 48.4 +/- 24.4, respectively (P = 0.02, ANOVA). Mean log CT-1 was higher in those with moderate/severe MR when compared to those without a significant regurgitant valvular lesion (P < 0.03). The only predictor of moderate/severe MR was log CT-1 (P = 0.004). Conclusion: These results sug gest that plasma CT-1 is raised in those patients with moderate/severe MR i n the presence of normal left ventricular systolic function. This secretion of CT-1 could potentially be the cause of ventricular dilatation and subse quent loss of contractile function in these patients. It also offers the in triguing possibility that plasma CT-1 could be used to monitor progression of mitral regurgitation biochemically. (C) European Society of Cardiology. All rights reserved.