[Circulating Adhesion Molecules (cICAM-1, LcVCAM-1) in Patients with Suspected Inflammatory Heart Muscle Disease]

Unlabelled: Some patients with non-ischemic heart failure show inflammatory changes in the myocardium which are thought to be of causal or pathogenetic relevance for the heart failure. The intercellular adhesion molecule-1 (ICAM-1) and the vascular adhesion molecule-1 (VCAM-1) are membrane proteins with receptor function from the immunoglobulin superfamily which mediate the vascular adhesion and transmigration of leucocytes into the tissue and undergo increased expression in chronic immunological-inflammatory processes. In addition to membrane-bound adhesion molecules, soluble forms can be detected in serum. In the present study we investigated the occurrence and the significance of circulating ICAM-1 and VCAM-1 in 71 patients with non-ischemic heart failure (47 M/24 F, mean age: 55 +/- 11 years).

Methods: Serum concentrations of cICAM-1 and cVCAM-1 were analyzed using ELISA-Kits. The severity of heart failure was assessed in accordance to the NYHA-classification and to hemodynamic parameters (mean pulmonary pressure, left ventricular ejection fraction). Inflammatory heart disease was assessed histologically and immunohistologically (T-lymphocytes > 7.0/mm2, increased expression of the histocompatibility antigens of class I and II) in right ventricular endomyocardial biopsies. 16 healthy, age-matched patients (8 M/8 F, mean age: 55 +/- 6 years, mean ejection fraction 76 +/- 3%) without signs of inflammation in the myocardium (mean T-lymphocytes < 3.5 cells/mm2, low expression of HLA-class I and II) served as controls.

Results: The mean serum concentrations of circulating ICAM-1 and VCAM-1 (cICAM-1, cVCAM-1) were higher in patients with non-ischemic heart failure (372 +/- 107 ng/ml and 949 +/- 439 ng/ml) than controls (264 +/- 37 and 710 +/- 164 ng/ml) (p < 0.05). The mean concentrations of both adhesion molecules varied as a function of the mean pulmonary pressure and the left ventricular ejection fracture (for cICAM-1: Pearson's r: 0.24 and -0.33, p < 0.05; for cVCAM-1: Pearson's r: 0.28 and -0.26, p < 0.05). In 38% (n = 16) of patients with elevated concentrations of cICAM-1 (> or = 337 ng/ml) and 41% (n = 7) of those with elevated serum levels of cVCAM-1 (> or = 1038 ng/ml), the myocardial biopsies showed increased lymphocytic infiltration between 7 and 22 T-lymphocytes/mm2 and an enhanced expression of the MHC antigens of class I/II as sign of an activated inflammatory process in the myocardium. All patients with more than 9.3 T-lymphocytes/mm2 in the myocardium (n = 7) had higher serum levels of cICAM-1 (447 +/- 146 ng/ml, p < 0.05 compared to controls) and of cVCAM-1 (1577 +/- 688 ng/ml, p < 0.001). Both adhesion molecules correlated significantly with the mean number of T-lymphocytes in the myocardium (Pearson's r: 0.31-0.37, p < 0.05).

Summary And Conclusion: The present study shows that the elevated levels of cICAM-1 and cVCAM-1 are often found in the serum of patients with non-ischemic heart failure. These raised serum levels correlate with inflammatory infiltrates in the myocardial tissue and with the clinical and hemodynamic signs of heart failure, thus, confirming a connection between heart failure and inflammatory changes in the myocardium.