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

Circulation. 2002 May 28;105(21):2512-7. doi: 10.1161/01.cir.0000017264.66561.3d.

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Biomarkers / blood
  • Biopsy
  • Blood Pressure / drug effects
  • Cluster Analysis
  • Collagen / analysis
  • Collagen / metabolism
  • Echocardiography, Doppler
  • Endomyocardial Fibrosis / complications
  • Endomyocardial Fibrosis / drug therapy*
  • Endomyocardial Fibrosis / physiopathology
  • Female
  • Heart Function Tests
  • Humans
  • Hypertension / classification
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Myocardium / metabolism
  • Myocardium / pathology
  • Peptide Fragments / blood
  • Procollagen / blood
  • Reference Values
  • Remission Induction
  • Treatment Outcome
  • Ventricular Dysfunction, Left / complications
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / physiopathology

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Peptide Fragments
  • Procollagen
  • procollagen type I carboxy terminal peptide
  • Collagen
  • Losartan