Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy: A pilot study

Hideo Izawa, Toyoaki Murohara, Kohzo Nagata, Satoshi Isobe, Hiroyuki Asano, Tetsuya Amano, Sahoko Ichihara, Tomoko Kato, Satoru Ohshima, Yosuke Murase, Shigeo Iino, Koji Obata, Akiko Noda, Kenji Okumura, Mitsuhiro Yokota

Research output: Contribution to journalArticle

158 Citations (Scopus)

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). Methods and 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 (≤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 PtP/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.

Original languageEnglish
Pages (from-to)2940-2945
Number of pages6
JournalCirculation
Volume112
Issue number19
DOIs
Publication statusPublished - 08-11-2005

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Mineralocorticoid Receptors
Dilated Cardiomyopathy
Left Ventricular Dysfunction
Spironolactone
Fibrosis
Collagen
Collagen Type I
Mineralocorticoid Receptor Antagonists
Biopsy
Collagen Type III
Doppler Echocardiography
Ventricular Pressure
Therapeutics
Serum
Left Ventricular Function
Heart Failure
Messenger RNA
Mortality

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Izawa, Hideo ; Murohara, Toyoaki ; Nagata, Kohzo ; Isobe, Satoshi ; Asano, Hiroyuki ; Amano, Tetsuya ; Ichihara, Sahoko ; Kato, Tomoko ; Ohshima, Satoru ; Murase, Yosuke ; Iino, Shigeo ; Obata, Koji ; Noda, Akiko ; Okumura, Kenji ; Yokota, Mitsuhiro. / Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy : A pilot study. In: Circulation. 2005 ; Vol. 112, No. 19. pp. 2940-2945.
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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). Methods and 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 (≤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 PtP/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.",
author = "Hideo Izawa and Toyoaki Murohara and Kohzo Nagata and Satoshi Isobe and Hiroyuki Asano and Tetsuya Amano and Sahoko Ichihara and Tomoko Kato and Satoru Ohshima and Yosuke Murase and Shigeo Iino and Koji Obata and Akiko Noda and Kenji Okumura and Mitsuhiro Yokota",
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Izawa, H, Murohara, T, Nagata, K, Isobe, S, Asano, H, Amano, T, Ichihara, S, Kato, T, Ohshima, S, Murase, Y, Iino, S, Obata, K, Noda, A, Okumura, K & Yokota, M 2005, 'Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy: A pilot study', Circulation, vol. 112, no. 19, pp. 2940-2945. https://doi.org/10.1161/CIRCULATIONAHA.105.571653

Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy : A pilot study. / Izawa, Hideo; Murohara, Toyoaki; Nagata, Kohzo; Isobe, Satoshi; Asano, Hiroyuki; Amano, Tetsuya; Ichihara, Sahoko; Kato, Tomoko; Ohshima, Satoru; Murase, Yosuke; Iino, Shigeo; Obata, Koji; Noda, Akiko; Okumura, Kenji; Yokota, Mitsuhiro.

In: Circulation, Vol. 112, No. 19, 08.11.2005, p. 2940-2945.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy

T2 - A pilot study

AU - Izawa, Hideo

AU - Murohara, Toyoaki

AU - Nagata, Kohzo

AU - Isobe, Satoshi

AU - Asano, Hiroyuki

AU - Amano, Tetsuya

AU - Ichihara, Sahoko

AU - Kato, Tomoko

AU - Ohshima, Satoru

AU - Murase, Yosuke

AU - Iino, Shigeo

AU - Obata, Koji

AU - Noda, Akiko

AU - Okumura, Kenji

AU - Yokota, Mitsuhiro

PY - 2005/11/8

Y1 - 2005/11/8

N2 - 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). Methods and 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 (≤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 PtP/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.

AB - 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). Methods and 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 (≤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 PtP/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.

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