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 (< 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.
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 DCMpatients 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-terminalpropeptide (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: Jochen Springer; Anika Tschirner; Arash Haghikia; Stephan von Haehling; Hind Lal; Aleksandra Grzesiak; Elena Kaschina; Sandra Palus; Mareike Pötsch; Karoline von Websky; Berthold Hocher; Celine Latouche; Frederic Jaisser; Lars Morawietz; Andrew J S Coats; John Beadle; Josep M Argiles; Thomas Thum; Gabor Földes; Wolfram Doehner; Denise Hilfiker-Kleiner; Thomas Force; Stefan D Anker Journal: Eur Heart J Date: 2013-08-29 Impact factor: 29.983
Authors: Tobias Täger; Clara Wiebalck; Hanna Fröhlich; Anna Corletto; Hugo A Katus; Lutz Frankenstein Journal: Clin Res Cardiol Date: 2017-08-04 Impact factor: 5.460
Authors: João Pedro Ferreira; António Barros; Bertram Pitt; Gilles Montalescot; Esteban Lopez de Sa; Christian W Hamm; Marcus Flather; Freek Verheugt; Harry Shi; Adelino Leite-Moreira; John Vincent; Patrick Rossignol; Faiez Zannad Journal: Clin Res Cardiol Date: 2018-09-27 Impact factor: 5.460