title: Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy: a pilot study.
abstract: BACKGROUND
  Mineralocorticoid receptor antagonism reduces mortality associated with heart failure by mechanisms that remain unclear. The effects of the mineralocorticoid receptor antagonist spironolactone on left ventricular (LV) function and chamber stiffness associated with myocardial fibrosis were investigated in mildly symptomatic patients with idiopathic dilated cardiomyopathy (DCM).
  
  
  RESULTS
  Twenty-five DCM patients with a New York Heart Association functional class of I or II were examined before and after treatment with spironolactone for 12 months. LV pressures and volumes were measured simultaneously, and LV endomyocardial biopsy specimens were obtained. Serum concentrations of the carboxyl-terminal propeptide (PIP) and carboxyl-terminal telopeptide (CITP) of collagen type I were measured. The patients were divided into 2 groups on the basis of the serum PIP/CITP ratio (< or =35, group A, n=12; >35, group B, n=13), an index of myocardial collagen accumulation. LV diastolic chamber stiffness, the collagen volume fraction, and abundance of collagen type I and III mRNAs in biopsy tissue were greater and the LV early diastolic strain rate (tissue Doppler echocardiography) was smaller in group B than in group A at baseline. These differences and the difference in PIP/CITP were greatly reduced after treatment of patients in group B with spironolactone, with treatment having no effect on these parameters in group A. The collagen volume fraction was significantly correlated with PIP/CITP, LV early diastolic strain rate, and LV diastolic chamber stiffness for all patients before and after treatment with spironolactone.
  
  
  CONCLUSIONS
  Spironolactone ameliorated LV diastolic dysfunction and reduced chamber stiffness in association with regression of myocardial fibrosis in mildly symptomatic patients with DCM. These effects appeared limited, however, to patients with increased myocardial collagen accumulation.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. izawa@med.nagoya-u.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Izawa
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Isobe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Asano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Amano
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kato
authors.forename: Satoru
authors.initials: S
authors.lastname: Ohshima
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Murase
authors.forename: Shigeo
authors.initials: S
authors.lastname: Iino
authors.forename: Koji
authors.initials: K
authors.lastname: Obata
authors.forename: Akiko
authors.initials: A
authors.lastname: Noda
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D010865:Pilot Projects; D013148:Spironolactone / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone