MEASURING EXTRACELLULAR-MATRIX TURNOVER IN THE SERUM OF PATIENTS WITHIDIOPATHIC OR ISCHEMIC DILATED CARDIOMYOPATHY AND IMPACT ON DIAGNOSISAND PROGNOSIS

Circulating levels of extracellular matrix components were measured by radioimmunoassays and tested if they were useful for clinical staging in chronic heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8 ischemic cases) the serum concentrations of proco llagen type III aminoterminal peptide (PIIINP), type I collagen telope ptide (ICTP), and basement membrane laminin were significantly higher then in 30 healthy controls regardless of the underlying etiology. Pat ients with serum values of PIIINP, ICTP, and laminin >7 mu g/L, 7.6 mu g/L, and 2.3 U/ml, respectively, were at higher relative risk for adv anced clinical stage, poor hemodynamic condition, hyponatremia, heart transplantation, and death during follow-up than patients with low lev els, with the exception that serum laminin > 2.3 U/ml was not signific antly associated with hyponatremia and heart transplantation. Despite their interdependence on liver function, circulating levels of PIIINP and ICTP were independent predictors of mortality. In 17 of the 41 pat ients with cardiomyopathy whose explanted hearts were available for hi stologic evaluation, serum PIIINP, ICTP, and laminin significantly cor related with the myocardial area fractions of their tissue analogues ( PIIINP vs myocardial collagen type iii, r = 0.784, p = 0.0013; serum I CTP vs myocardial collagen type I, r = 0.603, p 0.0527; and serum lami nin vs myocardial laminin, r = 0.605, p = 0.0411). In conclusion, the increase in extracellular matrix turnover, which may partially he deri ved From fibrosis in the myocardium, can be measured in the serum of p atients with dilated cardiomyopathy, and has on impact on risk stratif ication and prognosis.