Abstract 16910: Can Spironolactone Mitigate Myocardial Fibrosis and Alter Sudden Death Risk and Heart Failure Symptoms in Patients With Hypertrophic Cardiomyopathy?: A Prospective, Randomized Trial
Background: In hypertrophic cardiomyopathy (HCM), current therapies do not impact underlying disease pathology. Myocardial fibrosis assessed with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been implicated as a promoter of sudden death and heart failure. The mineralocorticoid aldosterone has been considered a mediator of fibrosis, and its blockade shown to normalize collagen content in mouse models of HCM.
Objective: We sought to determine if the mineralocorticoid receptor blocker spironolactone (a novel therapy for HCM) can decrease measures of myocardial fibrosis and improve clinical and imaging variables.
Methods: We randomized 53 HCM patients (41 ± 13 years old; 72% male) to double-blind treatment with spironolactone 50 mg daily or placebo for one year. Between these groups, we compared changes in serum markers of collagen synthesis (PINP and PIIINP), fibrosis by LGE (n=25), exercise capacity (peak VO2), diastolic function by echocardiography (septal E/e’) and heart failure symptoms at study entry and at 12 months.
Results: Measures of myocardial fibrosis were unchanged by spironolactone relative to placebo. The absolute difference, from baseline to follow-up, in serum markers of collagen synthesis and LGE, was not statistically different between the spironolactone and placebo groups (ΔPINP -1.4 vs.-1.4; p=1.0 and ΔPIIINP -2.8 vs. -3.0; p=0.8 and LGE: 0.8% vs 0.6%; p=0.7). Spironolactone also appeared to have no beneficial effect on a number of other relevant clinical variables, as the change at one year in all of these measures was not different in patients taking spironolactone compared with the placebo arm, including: Δpeak VO2 (-0.2 vs. +2.5 ml/kg-1/min-1; p=0.10), Δseptal E/e’ (-0.6 vs -0.7; p=1.0), Δmax LV wall thickness (-1.9 vs -2.1; p=0.94), and ΔNYHA class (p=0.9).
Conclusions: Spironolactone does not appear to alter markers of myocardial fibrosis or result in improvement in other relevant clinical markers, including heart failure symptoms. The aspiration of altering the HCM phenotype by pharmacologic mitigation of myocardial fibrosis does not seem likely with spironolactone, highlighting the importance of relying on the current risk algorithim and the ICD for primary prevention of sudden death.
- © 2013 by American Heart Association, Inc.