Effect of Spironolactone on Myocardial Fibrosis and Other Clinical Variables in Patients with Hypertrophic Cardiomyopathy



      Myocardial fibrosis has proved to be an important marker and determinant in the pathogenesis of hypertrophic cardiomyopathy. In particular, scar formation, if substantial, can promote ventricular tachyarrhythmias or progressive heart failure in the absence of left ventricular outflow obstruction. Therefore, an intervention to mitigate myocardial fibrosis would be potentially advantageous to hypertrophic cardiomyopathy patients.


      Eligible hypertrophic cardiomyopathy patients were randomized 1:1 in a prospective double-blind fashion to spironolactone 50 mg or placebo to be taken over a 12-month period. The primary endpoint was the effect of mineralocorticoid receptor blockade on serum markers of collagen synthesis and degradation. A number of other functional and morphologic variables and biomarkers comprised secondary exploratory measures.


      Fifty-three hypertrophic cardiomyopathypatients (41 ± 13 years old; 72% men) were randomized; demographic and clinical variable were well matched at baseline. Absolute change between baseline and 12 months did not differ between hypertrophic cardiomyopathy patients treated with spironolactone and those receiving placebo with respect to serum markers of collagen synthesis or degradation, fibrosis by late gadolinium enhancement on cardiac magnetic resonance imaging, or other clinical variables, including objective measure of functional capacity (peak VO2), New York Heart Association functional class, left ventricular wall thickness, mass and volume, and left atrial size, as well as assessment of diastolic function (P = .4-1.0).


      These findings do not support the use of spironolactone in hypertrophic cardiomyopathy to improve left ventricular remodeling by mitigating myocardial fibrosis or altering clinical course.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Maron B.J.
        • Ommen S.R.
        • Semsarian C.
        • et al.
        Hypertrophic cardiomyopathy: present and future, with transition into contemporary cardiovascular medicine.
        J Am Coll Cardiol. 2014; 64: 83-99
        • Chan R.H.
        • Maron B.J.
        • Olivotto I.
        • et al.
        Prognostic valve of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy.
        Circulation. 2014; 130: 484-495
        • Weng Z.
        • Yao J.
        • Chan R.H.
        • et al.
        Prognostic value of LGE-CMR in HCM: a meta-analysis.
        JACC Cardiovasc Imaging. 2016; 9: 1392-1402
        • Ho C.Y.
        • Lopez B.
        • Coelho-Filho O.R.
        • et al.
        Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy.
        N Eng J Med. 2010; 363: 552-563
        • Lim D.S.
        • Lutucuta S.
        • Bachireddy P.
        • et al.
        Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy.
        Circulation. 2001; 103: 789-791
        • Tsybouleva N.
        • Zhang L.
        • Chen S.
        • et al.
        Aldosterone, through novel signaling proteins, is a fundamental molecular bridge between the genetic defect and the cardiac phenotype of hypertrophic cardiomyopathy.
        Circulation. 2004; 109: 1284-1291
        • Pitt B.
        • Remme W.
        • Zannad F.
        • et al.
        Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.
        N Engl J Med. 2003; 348: 1309-1321
        • Pitt B.
        • Reichek N.
        • Willenbrock R.
        • et al.
        Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study.
        Circulation. 2003; 108: 1831-1838
        • The PEACE Trail Investigators
        Angiotensin-converting-enzyme inhibition in stable coronary artery disease.
        N Engl J Med. 2004; 351: 2058-2068
        • Pitt B.
        • Pfeffer M.A.
        • Assman S.F.
        • et al.
        Spironolactone for heart failure with preserved ejection fraction.
        N Engl J Med. 2014; 370: 1383-1392
        • Pfeffer M.A.
        • Claggett B.
        • Assman S.F.
        • et al.
        Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial.
        Circulation. 2015; 131: 34-42
        • Shirani J.
        • Pick R.
        • Roberts W.C.
        • et al.
        Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death.
        J Am Coll Cardiol. 2000; 35: 36-44
        • Zannad F.
        • Alla F.
        • Dousset B.
        • et al.
        Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators.
        Circulation. 2000; 102: 2700-2706
        • Querejeta R.
        • Lopez B.
        • Gonzalez A.
        • et al.
        Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis.
        Circulation. 2004; 110: 1263-1268
        • Axxelson A.
        • Iversen K.
        • Vejlstrop N.
        • et al.
        Efficacy and safety of the angiotensin II receptor blocker losartan in hypertrophic cardiomyopathy: the INHERIT randomized, double blind, placebo-controlled trial.
        Lancet Diabetes Endocrinol. 2015; 3: 123-131