P-181: Myocardial fibrosis determines left ventricular chamber stiffness in hypertensive patients. Effects of treatment with losartan

Experimental data suggest that myocardial fibrosis as a result of abnormal fibrillar collagen metabolism leads to increase in myocardial stiffness and decrease in ventrincular distensibility during diastole. On the other hand, chronic administration of losartan has been shown to induce diminution of collagen type I synthesis and regression of myocardial fibrosis in hypertensive patients. We, thus, have investigated whether alterations in collagen type I metabolism and myocardial collagen content are related to myocardial stiffness in hypertensives and whether treatment with losartan modifies myocardial stiffness. The study was performed in 34 patients with essential hypertension and hypertensive heart disease. Nineteen of these patients were also evaluated after 12 months of treatment with losartan. Right septal endomyocardial biopsies were performed to quantify collagen volume fraction (CVF). Left ventricular (LV) chamber stiffness (KLV) was determined from the deceleration time of the early mitral filling wave as measured echocardiographically. Serum concentrations of carboxy-terminal propeptide of collagen type I (PIP), a marker of collagen type I synthesis, and carboxy-terminal telopeptide of collagen type I (CITP), a marker of collagen type I degradation, were determined by radioimmunoassays. Histological analysis at baseline revealed the presence of 2 subgroups of patients: 8 with severe fibrosis and 26 with nonsevere fibrosis. Values of PIP:CITP ratio, CVF and KLV were significantly higher in the 2 subgroups of hypertensives than in normotensives. In addition, compared with patients with nonsevere fibrosis, patients with severe fibrosis exhibited values significantly increased of the PIP:CITP ratio, CVF and KLV. After treatment, the PIP:CITP ratio, CVF and KLV decreased significantly in patients with severe fibrosis (N=7). None of these parameters changed significantly after treatment in patients with nonsevere fibrosis (N=12). CVF was directly correlated with KLV (r=0.415, P < 0.02) in all hypertensives. These findings show a strong correlation between abnormal collagen type I metabolism, myocardial collagen content and LV chamber stiffness in patients with essential hypertension. Our results also suggest that the ability of losartan to improve collagen type I metabolism and induce regression of severe myocardial fibrosis is associated with diminution of myocardial stiffness in hypertensive patients. Thus, determination of KLV may be useful to asse