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 (K LV ) 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 K LV 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 K LV . After treatment, CVF and K LV 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 K LV ( 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.

Echocardiographic evaluation of diastolic heart failure

“…Neurohormonal modulation of the RAAS is currently the only therapy with some effect on the patho‐physiological mechanisms responsible for the increase in vascular and ventricular stiffness 185 , 186 . ACEIs 187 , 188 , ARBs 189 , and aldosterone receptor antagonists 190 , 191 , independent of their hemodynamic effects, mediate potentially favourable effects of reduced smooth muscle cell growth, prevention of collagen deposition, reduced growth factor expression, and regression of myocardial fibrosis. Spironolactone, an aldosterone antagonist, has also been shown to reduce myocardial fibrosis and thus may aid in the treatment of DD 192 .…”

Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart

“…[1][2][3] As excessive myocardial fibrosis is assumed to be a critical determinant of the deterioration of LV function 4,5 and the cause of arrhythmias, 6 regulating the proliferation and activation of fibroblasts would be an important therapeutic target in the disorder. The renin-angiotensin II (Ang II) system (RAS) is recognized to stimulate fibrosis, 7 whereas the inhibition of either angiotensin-converting enzyme (ACE) or Ang II type 1 receptor has been shown to regress myocardial fibrosis in patients with hypertensive heart disease.…”

Time course of serum collagen types I and III metabolism products after reperfused acute myocardial infarction in patients with and without systemic hypertension

“…[11][12][13][14] This excess of myocardial collagen is primarily a result of the uncoupling between increased synthesis and unchanged or decreased degradation of collagen type I fibres. 18 However, patients with coronary heart disease have been excluded from these studies, 11-14 so it is not clear if a different pattern of interstitial remodelling may be present in the first months after AMI in patients with antecedent hypertension.…”

“…[11][12][13][14] Accordingly, we serially measured serum products collagen types I and III turnover, which constitute the bulk of cardiac ECCM, 15 and LV volumes and function in a consecutive sample of patients successfully treated with primary percuta-neous coronary intervention (PCI) for a first AMI with LV systolic dysfunction. The purpose of this study was to evaluate if a different pattern of ECCM and LV remodelling is present in patients with antecedent hypertension compared with those without hypertension.…”