Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients

Abstract

Background - This study was designed to investigate whether myocardial collagen content is related to myocardial stiffness in patients with essential hypertension. Methods and Results - The study was performed in 34 patients with hypertensive heart disease. Nineteen of these patients were also evaluated after 12 months of treatment with losartan. Transvenous endomyocardial biopsies of the interventricular septum 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 by Doppler echocardiography. Histological analysis at baseline revealed the presence of 2 subgroups of patients: 8 with severe fibrosis and 26 with nonsevere fibrosis. Values of 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 significantly increased values of CVF and KLV. After treatment, 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. Conclusions - These findings show a strong association between myocardial collagen content and LV chamber stiffness in patients with essential hypertension. Our results also suggest that the ability of losartan to induce regression of severe myocardial fibrosis is associated with diminution of myocardial stiffness in hypertensive patients.