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

• Published in: The American journal of medicine Vol. 131; no. 7; pp. 837 - 841
• Main Authors: Maron, Martin S., Chan, Raymond H., Kapur, Navin K., Jaffe, Iris Z., McGraw, Adam P., Kerur, Raj, Maron, Barry J., Udelson, James E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018
• Subjects: Adult; Aldosterone inhibitor; Biomarkers - blood; Cardiomyopathy, Hypertrophic - diagnostic imaging; Cardiomyopathy, Hypertrophic - drug therapy; Cardiomyopathy, Hypertrophic - pathology; Collagen Type I - blood; Double-Blind Method; Fibrosis; Heart - diagnostic imaging; Heart - drug effects; Heart failure; Humans; Hypertrophic cardiomyopathy; Magnetic Resonance Imaging; Male; Mineralocorticoid Receptor Antagonists - therapeutic use; Myocardium - pathology; Peptide Fragments - blood; Procollagen - blood; Spironolactone - therapeutic use; Heart failure; Hypertrophic cardiomyopathy; Fibrosis; Aldosterone inhibitor
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/j.amjmed.2018.02.025

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.